<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01699022</url>
  </required_header>
  <id_info>
    <org_study_id>A09-109</org_study_id>
    <nct_id>NCT01699022</nct_id>
  </id_info>
  <brief_title>Pharmacokinetic and Pharmacodynamic Study of Cyclofem</brief_title>
  <official_title>Pharmacokinetic and Pharmacodynamic Study of Cyclofem</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sun Pharmaceutical Industries Limited</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sun Pharmaceutical Industries Limited</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Cyclofem® is a monthly injectable contraceptive containing 25 mg of medroxyprogesterone&#xD;
      acetate (MPA) and 5 mg of estradiol cypionate (E2C), a long-acting ester of estradiol. The&#xD;
      current study will assess the steady-state pharmacokinetics and pharmacodynamics of&#xD;
      medroxyprogesterone acetate (MPA) and estradiol (E2) after administration of Cyclofem® and&#xD;
      will provide critical information to determine similar bioavailability of Cyclofem to Lunelle&#xD;
      in women residing in the United States of America.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Concept Foundation, an international nonprofit organization based in Bangkok, Thailand, was&#xD;
      given the commercial rights to Cyclofem® by the World Health Organization (WHO) for use&#xD;
      internationally. The brand names that the Concept Foundation has registered internationally&#xD;
      include Cyclofem®, and Novafem® (Pharmacia Pharmaceuticals, Peapack NJ, formerly (Pharmacia&#xD;
      and Upjohn of Kalamazoo, Michigan). The company launched its product under license from&#xD;
      Concept Foundation with their own brand name, Lunelle™ in the US market. Lunelle™ was&#xD;
      approved by the Food and Drug Administration (FDA) in October, 2000 following which&#xD;
      approximately 350,000 women had used the product. However, following the acquisition of&#xD;
      Pharmacia and Upjohn by Pfizer and due to several production problems, Pfizer withdrew&#xD;
      Lunelle™ from the United States (US) market. Concept Foundation has licensed Sun&#xD;
      Pharmaceutical Industries Ltd, Mumbai, India to manufacture and market Cyclofem® in India and&#xD;
      other developing countries. United States Food and Drug Administration (US FDA) approval of&#xD;
      Cyclofem® is pivotal to the ultimate acceptance of such products in many countries because of&#xD;
      the rigorous standards applied by the Food and Drug Administration (FDA) for drug safety and&#xD;
      efficacy. This initial pharmacokinetic (PK) study is the first step on the road to Food and&#xD;
      Drug Administration (FDA) approval with the ultimate goal to expand the access and range of&#xD;
      methods available to women in the public sector. Approval of Cyclofem® by the United States&#xD;
      Food and Drug Administration (US FDA) would also allow the reintroduction of CICs to the&#xD;
      United States (US) market.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>June 2010</start_date>
  <completion_date type="Actual">December 2011</completion_date>
  <primary_completion_date type="Actual">July 2011</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Medroxyprogesterone Acetate (MPA) Concentrations</measure>
    <time_frame>&quot;Day 1&quot;, &quot;Day 29&quot;, &quot;Day 57' and 'Day 85&quot;</time_frame>
    <description>Assessment of mean trough levels of medroxyprogesterone acetate (MPA) on Day 1, Day 29, Day 57 and Day 85</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Medroxyprogesterone Acetate (MPA) Pharmacokinetics</measure>
    <time_frame>&quot;Day 85&quot;</time_frame>
    <description>The mean serum concentration-time profile for medroxyprogesterone acetate (MPA) after three consecutive monthly intramuscular administration of Cyclofem (AUC). Peripheral blood sample for MPA was to be drawn three times a week for PK assessment during the third treatment month (Days 58, 60, 62, 64, 67, 69, 71, 75, 78, and 85) and for Day 85 (28 days post 3rd dose).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Medroxyprogesterone Acetate (MPA) Pharmacokinetics Cmax</measure>
    <time_frame>85 days</time_frame>
    <description>The mean serum concentration-time profile for medroxyprogesterone acetate (MPA) after three consecutive monthly intramuscular administration of Cyclofem</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Medroxyprogesterone Acetate (MPA) Pharmacokinetics Tmax</measure>
    <time_frame>&quot;Day 85&quot;</time_frame>
    <description>Mean serum medroxyprogesterone acetate (MPA) concentrations peaked at 4.1 days (range 1 - 21 days) after the third monthly administration of Cyclofem.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Medroxyprogesterone Acetate (MPA) Pharmacokinetics T1/2</measure>
    <time_frame>&quot;Day 85&quot;</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Estradiol (E2) Concentrations</measure>
    <time_frame>&quot;Day 1&quot;, &quot;Day 29&quot;, &quot;Day 57' and ''Day 85&quot;</time_frame>
    <description>Mean serum estradiol (E2) concentrations on Day 1, Day 29, Day 57 and Day 85</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Estradiol (E2) Pharmacokinetics.</measure>
    <time_frame>Day 28</time_frame>
    <description>AUC 0-28, AUC(0-inf). Peripheral blood sample for E2 was to be drawn three times a week for PK assessment during the third treatment month.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Tmax</measure>
    <time_frame>&quot;Day 85&quot;</time_frame>
    <description>Mean serum concentrations of estradiol (E2) peaked by 3.3 days (range 1 - 7 days) following the third monthly injection</description>
  </primary_outcome>
  <primary_outcome>
    <measure>T1/2</measure>
    <time_frame>&quot;Day 85&quot;</time_frame>
    <description>Mean no of days for medroxyprogesterone acetate (MPA) and estradiol (E2)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants Who Achieved Ovulation Determined by Serum Progesterone Concentration</measure>
    <time_frame>Day 134</time_frame>
    <description>Return of ovulation measured by changes in serum progesterone concentration by&#xD;
analysis on Day 18, Day 21 (Control cycle), Day 103, Day 106, Day 131 and Day 134 indicating the number of subjects who achieved ovulation.&#xD;
Outcome measure description indicates what was measure.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">17</enrollment>
  <condition>Contraception</condition>
  <arm_group>
    <arm_group_label>Injection Cyclofem</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Injection of Cyclofem contains 25 mg medroxyprogesterone acetate (MPA) and 5 mg estradiol cypionate as a microcrystalline suspension in 0.5ml aqueous solution and is supplied in vials.&#xD;
Women were administered three consecutive monthly injections of Cyclofem for prevention of ovulation, and were followed until the 92nd day from the last (third) injection.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Injection Cyclofem</intervention_name>
    <description>Injection Cyclofem contains 25 mg medroxyprogesterone acetate (MPA) and 5 mg estradiol cypionate as a microcrystalline suspension in 0.5ml aqueous solution and is supplied in vials.&#xD;
Women were administered three consecutive monthly injections of Cyclofem for prevention of ovulation, and were followed until the 92nd day from the last (third) injection.</description>
    <arm_group_label>Injection Cyclofem</arm_group_label>
    <other_name>Cyclofem</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Between 18 and 45 years of age, inclusive;&#xD;
&#xD;
          2. In good health, as evidenced by history and procedures at screening/enrollment visit&#xD;
&#xD;
          3. Without any clinically significant systemic disease;&#xD;
&#xD;
          4. Not at risk for pregnancy, having undergone surgical sterilization&#xD;
&#xD;
          5. Have had regular menstrual cycles (every 21-35 days) for the past two cycles;&#xD;
&#xD;
          6. Planning to reside in the area for at least 7 months after enrolling in the study; and&#xD;
&#xD;
          7. Willing and able to comply with study procedures&#xD;
&#xD;
          8. Have a body mass index (BMI) between 18 and 30 inclusive.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Contraindications to the use of Cyclofem® include:&#xD;
&#xD;
               1. Smoking any number of cigarettes per day in a woman &gt; 35 years old (or in a woman&#xD;
                  34 years-old who will turn 35 years-old during the study),&#xD;
&#xD;
               2. Symptoms of chest pain or shortness of breath,&#xD;
&#xD;
               3. Screening visit blood pressure &gt;140/90, (subjects on hypertensive medications, in&#xD;
                  good blood pressure control will be admitted).&#xD;
&#xD;
               4. Past or current thrombophlebitis or thromboembolic disorders,&#xD;
&#xD;
               5. Past or current cerebral vascular or coronary artery disease&#xD;
&#xD;
               6. History of stroke, myocardial infarction or ischemic heart disease or complicated&#xD;
                  valvular heart disease&#xD;
&#xD;
               7. Diabetes&#xD;
&#xD;
               8. Past or current carcinoma of the endometrium cervix or vagina; breast or other&#xD;
                  known or suspected estrogen-depended neoplasia,&#xD;
&#xD;
               9. Headaches with focal neurological symptoms,&#xD;
&#xD;
              10. Unexplained abnormal vaginal bleeding,&#xD;
&#xD;
              11. Liver dysfunction or disease, such as a history of hepatic adenoma or carcinoma;&#xD;
                  history of cholestatic jaundice of pregnancy or jaundice with prior hormonal&#xD;
                  contraceptive use including severe pruritus of pregnancy, severe cirrhosis, or&#xD;
                  active hepatitis (defined as aspartate aminotransferase [AST or SGOT ≥ 120 IU/L]&#xD;
                  or alanine aminotransferase [ALT or SGPT ≥ 135 IU/L]) or clinically significant&#xD;
                  laboratory abnormalities as judged by the physician evaluating the individual&#xD;
                  subject).&#xD;
&#xD;
          2. Known hypersensitivity to any component of Cyclofem®&#xD;
&#xD;
          3. Have an abnormal Pap smear in the past 12 months defined as:&#xD;
&#xD;
               1. Atypical squamous cells of undetermined significance (ASC-US) without a normal&#xD;
                  repeat Pap smear at least 6 months later;&#xD;
&#xD;
               2. Atypical squamous cells of undetermined significance (ASC-US) with positive&#xD;
                  reflex high-risk human papillomavirus (HPV) testing (Atypical squamous cells of&#xD;
                  undetermined significance [ASC-US]/human papillomavirus [HPV]+) or low-grade&#xD;
                  squamous intraepithelial lesion (LSIL) except when a colposcopy was performed&#xD;
                  (with or without biopsy) and found no evidence of high-grade disease (cervical&#xD;
                  intraepithelial neoplasia [CIN II] or worse) unless treatment is indicated per&#xD;
                  local standard of care;&#xD;
&#xD;
               3. ASC-H, atypical glandular cells, or high grade squamous intraepithelial lesion&#xD;
                  (HSIL) unless treatment was received and follow-up at least 6 months after the&#xD;
                  treatment showed no evidence of disease; malignant cells;&#xD;
&#xD;
          4. Current use of rifampin, griseofulvin, phenytoin, carbamazepine, barbiturates, or&#xD;
             primidone;&#xD;
&#xD;
          5. Other conditions that, in the opinion of the investigator, would constitute&#xD;
             contraindications to participation in the study or would compromise ability to comply&#xD;
             with the study protocol, such as any major chronic illness including cancer, serious&#xD;
             autoimmune disease or a major psychiatric disorder (e.g. schizophrenia);&#xD;
&#xD;
          6. Current participation in any other drug or device study, or any study which, in the&#xD;
             opinion of the investigator, would jeopardize interpretation of results of this study;&#xD;
&#xD;
          7. Active thyroid disease as measured by thyroid-stimulating hormone [TSH] levels ≤0.3&#xD;
             mU/L or ≥ 5 mU/L. Subjects with thyroid disease in good control with thyroid&#xD;
             medication will be admitted.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>David F Archer, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Director, Conrad Clinical Research Center.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Clinical Research Center Norfolk, Virginia 601 Colley Avenue,</name>
      <address>
        <city>Norfolk</city>
        <state>Virginia</state>
        <zip>23507</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>September 28, 2012</study_first_submitted>
  <study_first_submitted_qc>October 2, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 3, 2012</study_first_posted>
  <results_first_submitted>December 12, 2012</results_first_submitted>
  <results_first_submitted_qc>December 27, 2013</results_first_submitted_qc>
  <results_first_posted type="Estimate">December 30, 2013</results_first_posted>
  <last_update_submitted>August 19, 2020</last_update_submitted>
  <last_update_submitted_qc>August 19, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 2, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Contraceptive</keyword>
  <keyword>Injectable</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>CycloProvera</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The study was conducted at the CONRAD Clinical Research Center (CRC) located in the Jones Institute for Reproductive Medicine at the Eastern Virginia Medical School (EVMS) in Norfolk, vasectomy (VA) in subjects with previous surgical sterilization and therefore were not at risk for pregnancy</recruitment_details>
      <pre_assignment_details>A total of 7 women failed screening: 3 women had control cycle luteal phase serum P &lt; 3 ng/mL; 3 women withdrew consent; and 1 potential subject was not enrolled because the study had enrolled the requisite number of subjects and was closed for enrollment</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Injection Cyclofem</title>
          <description>Injection of Cyclofem contains 25 mg medroxyprogesterone acetate (MPA) and 5 mg estradiol cypionate as a microcrystalline suspension in 0.5ml aqueous solution and is supplied in vials.&#xD;
Women were administered three consecutive monthly injections of Cyclofem for prevention of ovulation, and were followed until the 92nd day from the last (third) injection.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="17"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Early discontinuation from the study</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Injection Cyclofem</title>
          <description>Injection of Cyclofem contains 25 mg medroxyprogesterone acetate (MPA) and 5 mg estradiol cypionate as a microcrystalline suspension in 0.5ml aqueous solution and is supplied in vials.&#xD;
Women were administered three consecutive monthly injections of Cyclofem for prevention of ovulation, and were followed until the 92nd day from the last (third) injection.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="17"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="34.8" spread="5.21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Medroxyprogesterone Acetate (MPA) Concentrations</title>
        <description>Assessment of mean trough levels of medroxyprogesterone acetate (MPA) on Day 1, Day 29, Day 57 and Day 85</description>
        <time_frame>&quot;Day 1&quot;, &quot;Day 29&quot;, &quot;Day 57' and 'Day 85&quot;</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Injection Cyclofem</title>
            <description>Injection of Cyclofem contains 25 mg medroxyprogesterone acetate (MPA) and 5 mg estradiol cypionate as a microcrystalline suspension in 0.5ml aqueous solution and is supplied in vials.&#xD;
Women were administered three consecutive monthly injections of Cyclofem for prevention of ovulation, and were followed until the 92nd day from the last (third) injection.</description>
          </group>
        </group_list>
        <measure>
          <title>Medroxyprogesterone Acetate (MPA) Concentrations</title>
          <description>Assessment of mean trough levels of medroxyprogesterone acetate (MPA) on Day 1, Day 29, Day 57 and Day 85</description>
          <units>ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.00" spread="0.02"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 29</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.27" spread="0.09"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 57</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.43" spread="0.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 85</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.44" spread="0.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Medroxyprogesterone Acetate (MPA) Pharmacokinetics</title>
        <description>The mean serum concentration-time profile for medroxyprogesterone acetate (MPA) after three consecutive monthly intramuscular administration of Cyclofem (AUC). Peripheral blood sample for MPA was to be drawn three times a week for PK assessment during the third treatment month (Days 58, 60, 62, 64, 67, 69, 71, 75, 78, and 85) and for Day 85 (28 days post 3rd dose).</description>
        <time_frame>&quot;Day 85&quot;</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cyclofem</title>
          </group>
        </group_list>
        <measure>
          <title>Medroxyprogesterone Acetate (MPA) Pharmacokinetics</title>
          <description>The mean serum concentration-time profile for medroxyprogesterone acetate (MPA) after three consecutive monthly intramuscular administration of Cyclofem (AUC). Peripheral blood sample for MPA was to be drawn three times a week for PK assessment during the third treatment month (Days 58, 60, 62, 64, 67, 69, 71, 75, 78, and 85) and for Day 85 (28 days post 3rd dose).</description>
          <units>ng*day/mL</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AUC (0-84)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31.5029" spread="7.49456"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AUC (0-28)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20.5831" spread="6.58448"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AUC (0-inf)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33.4528" spread="8.23617"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Medroxyprogesterone Acetate (MPA) Pharmacokinetics Cmax</title>
        <description>The mean serum concentration-time profile for medroxyprogesterone acetate (MPA) after three consecutive monthly intramuscular administration of Cyclofem</description>
        <time_frame>85 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cyclofem</title>
          </group>
        </group_list>
        <measure>
          <title>Medroxyprogesterone Acetate (MPA) Pharmacokinetics Cmax</title>
          <description>The mean serum concentration-time profile for medroxyprogesterone acetate (MPA) after three consecutive monthly intramuscular administration of Cyclofem</description>
          <units>ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.311380" spread="0.437259"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Medroxyprogesterone Acetate (MPA) Pharmacokinetics Tmax</title>
        <description>Mean serum medroxyprogesterone acetate (MPA) concentrations peaked at 4.1 days (range 1 - 21 days) after the third monthly administration of Cyclofem.</description>
        <time_frame>&quot;Day 85&quot;</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cyclofem</title>
          </group>
        </group_list>
        <measure>
          <title>Medroxyprogesterone Acetate (MPA) Pharmacokinetics Tmax</title>
          <description>Mean serum medroxyprogesterone acetate (MPA) concentrations peaked at 4.1 days (range 1 - 21 days) after the third monthly administration of Cyclofem.</description>
          <units>day</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.1" spread="5.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Medroxyprogesterone Acetate (MPA) Pharmacokinetics T1/2</title>
        <time_frame>&quot;Day 85&quot;</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cyclofem</title>
          </group>
        </group_list>
        <measure>
          <title>Medroxyprogesterone Acetate (MPA) Pharmacokinetics T1/2</title>
          <units>day</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.9413" spread="7.49264"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Estradiol (E2) Concentrations</title>
        <description>Mean serum estradiol (E2) concentrations on Day 1, Day 29, Day 57 and Day 85</description>
        <time_frame>&quot;Day 1&quot;, &quot;Day 29&quot;, &quot;Day 57' and ''Day 85&quot;</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cyclofem</title>
          </group>
        </group_list>
        <measure>
          <title>Estradiol (E2) Concentrations</title>
          <description>Mean serum estradiol (E2) concentrations on Day 1, Day 29, Day 57 and Day 85</description>
          <units>pg/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="46" spread="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 29</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44" spread="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 57</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="52" spread="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 85</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="42" spread="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Estradiol (E2) Pharmacokinetics.</title>
        <description>AUC 0-28, AUC(0-inf). Peripheral blood sample for E2 was to be drawn three times a week for PK assessment during the third treatment month.</description>
        <time_frame>Day 28</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Injection Cyclofem</title>
            <description>Injection of Cyclofem contains 25 mg medroxyprogesterone acetate (MPA) and 5 mg estradiol cypionate as a microcrystalline suspension in 0.5ml aqueous solution and is supplied in vials.&#xD;
Women were administered three consecutive monthly injections of Cyclofem for prevention of ovulation, and were followed until the 92nd day from the last (third) injection.</description>
          </group>
        </group_list>
        <measure>
          <title>Estradiol (E2) Pharmacokinetics.</title>
          <description>AUC 0-28, AUC(0-inf). Peripheral blood sample for E2 was to be drawn three times a week for PK assessment during the third treatment month.</description>
          <units>pg*day/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AUC (0-28)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3289.6546" spread="888.56879"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AUC (0-inf)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3922.3365" spread="1019.80283"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Tmax</title>
        <description>Mean serum concentrations of estradiol (E2) peaked by 3.3 days (range 1 - 7 days) following the third monthly injection</description>
        <time_frame>&quot;Day 85&quot;</time_frame>
        <population>Tmax</population>
        <group_list>
          <group group_id="O1">
            <title>Cyclofem</title>
          </group>
        </group_list>
        <measure>
          <title>Tmax</title>
          <description>Mean serum concentrations of estradiol (E2) peaked by 3.3 days (range 1 - 7 days) following the third monthly injection</description>
          <population>Tmax</population>
          <units>day</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.3" spread="2.49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>T1/2</title>
        <description>Mean no of days for medroxyprogesterone acetate (MPA) and estradiol (E2)</description>
        <time_frame>&quot;Day 85&quot;</time_frame>
        <population>Tmax</population>
        <group_list>
          <group group_id="O1">
            <title>Cyclofem</title>
          </group>
        </group_list>
        <measure>
          <title>T1/2</title>
          <description>Mean no of days for medroxyprogesterone acetate (MPA) and estradiol (E2)</description>
          <population>Tmax</population>
          <units>day</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>medroxyprogesterone acetate (MPA)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.9413" spread="7.49264"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Estradiol (E2)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.0960" spread="4.87120"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants Who Achieved Ovulation Determined by Serum Progesterone Concentration</title>
        <description>Return of ovulation measured by changes in serum progesterone concentration by&#xD;
analysis on Day 18, Day 21 (Control cycle), Day 103, Day 106, Day 131 and Day 134 indicating the number of subjects who achieved ovulation.&#xD;
Outcome measure description indicates what was measure.</description>
        <time_frame>Day 134</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cyclofem</title>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Achieved Ovulation Determined by Serum Progesterone Concentration</title>
          <description>Return of ovulation measured by changes in serum progesterone concentration by&#xD;
analysis on Day 18, Day 21 (Control cycle), Day 103, Day 106, Day 131 and Day 134 indicating the number of subjects who achieved ovulation.&#xD;
Outcome measure description indicates what was measure.</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 18</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 21</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 103</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 106</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 131</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 134</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>The subjects were assessed for incidence of adverse events up to Day 92 (during the control and treatment period, and up to Day 134 (during the follow-up period)</time_frame>
      <desc>Toxicities and AEs were summarized by severity and relationship to treatment. Clinical laboratory parameters and vital signs were summarized as changes and shifts from baseline to final on treatment assignment and by clinically significant abnormalities. Vital signs during study drug dosing were summarized as changes from baseline.</desc>
      <group_list>
        <group group_id="E1">
          <title>Injection Cyclofem</title>
          <description>Injection of Cyclofem contains 25 mg medroxyprogesterone acetate (MPA) and 5 mg estradiol cypionate as a microcrystalline suspension in 0.5ml aqueous solution and is supplied in vials.&#xD;
Women were administered three consecutive monthly injections of Cyclofem for prevention of ovulation, and were followed until the 92nd day from the last (third) injection.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>Menorrhagia</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title vocab="Vaginitis bacterial">Vaginitis bacterial</sub_title>
                <counts group_id="E1" events="7" subjects_affected="2" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Menorrhagia</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Shravanti Bhowmik</name_or_title>
      <organization>SPARC</organization>
      <phone>02266455645 ext 5626</phone>
      <email>shravanti.bhowmik@sparcmail.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01699022
org study id: A09-109
nct id: NCT01699022
lead sponsor: 
has dmc: No
Cyclofem® is a monthly injectable contraceptive containing 25 mg of medroxyprogesterone
      acetate (MPA) and 5 mg of estradiol cypionate (E2C), a long-acting ester of estradiol. The
      current study will assess the steady-state pharmacokinetics and pharmacodynamics of
      medroxyprogesterone acetate (MPA) and estradiol (E2) after administration of Cyclofem® and
      will provide critical information to determine similar bioavailability of Cyclofem to Lunelle
      in women residing in the United States of America.
Concept Foundation, an international nonprofit organization based in Bangkok, Thailand, was
      given the commercial rights to Cyclofem® by the World Health Organization (WHO) for use
      internationally. The brand names that the Concept Foundation has registered internationally
      include Cyclofem®, and Novafem® (Pharmacia Pharmaceuticals, Peapack NJ, formerly (Pharmacia
      and Upjohn of Kalamazoo, Michigan). The company launched its product under license from
      Concept Foundation with their own brand name, Lunelle™ in the US market. Lunelle™ was
      approved by the Food and Drug Administration (FDA) in October, 2000 following which
      approximately 350,000 women had used the product. However, following the acquisition of
      Pharmacia and Upjohn by Pfizer and due to several production problems, Pfizer withdrew
      Lunelle™ from the United States (US) market. Concept Foundation has licensed Sun
      Pharmaceutical Industries Ltd, Mumbai, India to manufacture and market Cyclofem® in India and
      other developing countries. United States Food and Drug Administration (US FDA) approval of
      Cyclofem® is pivotal to the ultimate acceptance of such products in many countries because of
      the rigorous standards applied by the Food and Drug Administration (FDA) for drug safety and
      efficacy. This initial pharmacokinetic (PK) study is the first step on the road to Food and
      Drug Administration (FDA) approval with the ultimate goal to expand the access and range of
      methods available to women in the public sector. Approval of Cyclofem® by the United States
      Food and Drug Administration (US FDA) would also allow the reintroduction of CICs to the
      United States (US) market.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Medroxyprogesterone Acetate (MPA) Concentrations
time frame: "Day 1", "Day 29", "Day 57' and 'Day 85"
description: Assessment of mean trough levels of medroxyprogesterone acetate (MPA) on Day 1, Day 29, Day 57 and Day 85
measure: Medroxyprogesterone Acetate (MPA) Pharmacokinetics
time frame: "Day 85"
description: The mean serum concentration-time profile for medroxyprogesterone acetate (MPA) after three consecutive monthly intramuscular administration of Cyclofem (AUC). Peripheral blood sample for MPA was to be drawn three times a week for PK assessment during the third treatment month (Days 58, 60, 62, 64, 67, 69, 71, 75, 78, and 85) and for Day 85 (28 days post 3rd dose).
measure: Medroxyprogesterone Acetate (MPA) Pharmacokinetics Cmax
time frame: 85 days
description: The mean serum concentration-time profile for medroxyprogesterone acetate (MPA) after three consecutive monthly intramuscular administration of Cyclofem
measure: Medroxyprogesterone Acetate (MPA) Pharmacokinetics Tmax
time frame: "Day 85"
description: Mean serum medroxyprogesterone acetate (MPA) concentrations peaked at 4.1 days (range 1 - 21 days) after the third monthly administration of Cyclofem.
measure: Medroxyprogesterone Acetate (MPA) Pharmacokinetics T1/2
time frame: "Day 85"
measure: Estradiol (E2) Concentrations
time frame: "Day 1", "Day 29", "Day 57' and ''Day 85"
description: Mean serum estradiol (E2) concentrations on Day 1, Day 29, Day 57 and Day 85
measure: Estradiol (E2) Pharmacokinetics.
time frame: Day 28
description: AUC 0-28, AUC(0-inf). Peripheral blood sample for E2 was to be drawn three times a week for PK assessment during the third treatment month.
measure: Tmax
time frame: "Day 85"
description: Mean serum concentrations of estradiol (E2) peaked by 3.3 days (range 1 - 7 days) following the third monthly injection
measure: T1/2
time frame: "Day 85"
description: Mean no of days for medroxyprogesterone acetate (MPA) and estradiol (E2)
measure: Number of Participants Who Achieved Ovulation Determined by Serum Progesterone Concentration
time frame: Day 134
description: Return of ovulation measured by changes in serum progesterone concentration by
analysis on Day 18, Day 21 (Control cycle), Day 103, Day 106, Day 131 and Day 134 indicating the number of subjects who achieved ovulation.
Outcome measure description indicates what was measure.
arm group label: Injection Cyclofem
arm group type: Experimental
description: Injection of Cyclofem contains 25 mg medroxyprogesterone acetate (MPA) and 5 mg estradiol cypionate as a microcrystalline suspension in 0.5ml aqueous solution and is supplied in vials.
Women were administered three consecutive monthly injections of Cyclofem for prevention of ovulation, and were followed until the 92nd day from the last (third) injection.
intervention type: Drug
intervention name: Injection Cyclofem
description: Injection Cyclofem contains 25 mg medroxyprogesterone acetate (MPA) and 5 mg estradiol cypionate as a microcrystalline suspension in 0.5ml aqueous solution and is supplied in vials.
Women were administered three consecutive monthly injections of Cyclofem for prevention of ovulation, and were followed until the 92nd day from the last (third) injection.
arm group label: Injection Cyclofem
other name: Cyclofem
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: David F Archer, MD
role: Principal Investigator
affiliation: Director, Conrad Clinical Research Center.
facility: 
country: United States
responsible party type: Sponsor
mesh term: CycloProvera
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 