<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/NCT01690052</url>
  </required_header>
  <id_info>
    <org_study_id>9999</org_study_id>
    <nct_id>NCT01690052</nct_id>
  </id_info>
  <brief_title>Efficacy of Cevimeline Versus Pilocarpine in the Secretion of Saliva</brief_title>
  <official_title>Efficacy of Cevimeline vs. Pilocarpine in the Secretion of Saliva</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Kentucky</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Kentucky</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The main objectives were: 1) To determine the efficacy of both cevimeline and pilocarpine in&#xD;
      the secretion of saliva in patients with xerostomia, and 2) To compare the side-effects&#xD;
      between the treatment for xerostomia with cevimeline and with pilocarpine.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Pilocarpine is a cholinergic agonist with predominant muscarinic action.As such, it acts at&#xD;
      muscarinic-cholinergic receptors found throughout the body and promotes fluid secretion. Due&#xD;
      to this, one of the main side-effects of pilocarpine is an increased amount of sweating.&#xD;
      Thus, not only are the salivary glands stimulated, but all of the body's exocrine glands'&#xD;
      production is heightened. On the other hand, cevimeline is a drug with a high affinity for&#xD;
      specific muscarinic receptors (M3) located on lachrymal and salivary gland epithelium. At&#xD;
      least in theory, cevimeline will produce less side effects compared with pilocarpine because&#xD;
      of the higher affinity for the muscarinic receptors located in the salivary glands. A limited&#xD;
      number of human clinical trials in the efficacy of cevimeline and pilocarpine to increase the&#xD;
      production of saliva and the side effects have been performed with no conclusive results.&#xD;
&#xD;
      The main purposes of this study were to determine the efficacy of cevimeline and pilocarpine&#xD;
      in the secretion of saliva in patients with xerostomia, and to compare the side-effects&#xD;
      between these two medications.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2009</start_date>
  <completion_date type="Actual">July 2010</completion_date>
  <primary_completion_date type="Actual">June 2010</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline in Saliva Production in ml.</measure>
    <time_frame>4 weeks</time_frame>
    <description>The primary outcome measure was the change of stimulated and non-stimulated saliva in ml from the baseline record.&#xD;
At each appointment (weekly), participants will provide 2 saliva samples to measure their current salivary output. The first measurement will be obtained by having the patient spit as much as he or she could into a cup for five minutes. The amount of saliva in ml will be recorded.&#xD;
The second measurement will be obtained in a similar manner with the addition of having the patient chew on a block of unflavored wax. Patients will complete weekly questionnaires to help determine which side-effects they experience as they take the medications.</description>
  </primary_outcome>
  <other_outcome>
    <measure>Adverse Events</measure>
    <time_frame>four weeks</time_frame>
    <description>Adverse events related to the combination and order of study medication will be measured</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">15</enrollment>
  <condition>Dry Mouth</condition>
  <arm_group>
    <arm_group_label>Cevimeline</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Cevimeline vs Pilocarpine</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Pilocarpine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Pilocarpine vs. Cevimeline</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cevimeline</intervention_name>
    <description>Cevimlenine Vs Pilocarpine, cross over design. Two sequences were evaluated &quot;cevimeline first, then pilocarpine&quot; and &quot;pilocarpine first, then cevimeline&quot;. Each sequence was evaluated for 4 weeks with one week &quot;washout&quot; period in between both sequences. 15 patients were randomly assigned to a specific sequence by a research pharmacist independent from the study authors. The patients received 30mg of cevimeline three times a day and pilocarpine 5mg three times a day.</description>
    <arm_group_label>Cevimeline</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pilocarpine</intervention_name>
    <description>Cevimlenine Vs Pilocarpine, cross over design, 4 weeks, one week wash out</description>
    <arm_group_label>Pilocarpine</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Potential candidates with the diagnosis of moderate-severe xerostomia were identified from&#xD;
        the Oral Medicine Clinic at the University Of Kentucky College Of Dentistry, or self&#xD;
        referrals in response to IRB approved study announcements. Enrollment required no clinical&#xD;
        evidence of oral lesions, subjective perception of dry mouth and less than 2 mL of saliva&#xD;
        collected in 5 minutes without stimulation. Exclusion criteria included patients with non&#xD;
        controlled chronic obstructive pulmonary disease (COPD), depression, asthma, cardiac&#xD;
        arrhythmias, glaucoma, and the current use of any medication with interactions with&#xD;
        cevimeline and pilocarpine.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Joel Thompson, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Kentucky</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Kentucky Orofacial Pain Center College of Dentistry</name>
      <address>
        <city>Lexington</city>
        <state>Kentucky</state>
        <zip>40536</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2018</verification_date>
  <study_first_submitted>April 6, 2011</study_first_submitted>
  <study_first_submitted_qc>September 17, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 21, 2012</study_first_posted>
  <results_first_submitted>December 16, 2012</results_first_submitted>
  <results_first_submitted_qc>August 5, 2014</results_first_submitted_qc>
  <results_first_posted type="Estimate">August 6, 2014</results_first_posted>
  <last_update_submitted>May 1, 2018</last_update_submitted>
  <last_update_submitted_qc>May 1, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">June 4, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Kentucky</investigator_affiliation>
    <investigator_full_name>Joel Thompson, PhD</investigator_full_name>
    <investigator_title>PRS administrator</investigator_title>
  </responsible_party>
  <keyword>dry mouth</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Xerostomia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pilocarpine</mesh_term>
    <mesh_term>Cevimeline</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Patients were recruited from the Salivary Gland Dysfunction Clinic at the U. of K. A cross-over double-blind randomized trial was designed. Two arms were assembled. First arm the SEQUENCE was cevimeline(C) then pilocarpine(P), and for the second the SEQUENCE was P then C. Each participant received the drug for 4 weeks with 1 week washout period.</recruitment_details>
      <pre_assignment_details>The total number of patients screened for the study was 28. Of 28 patients, 15 met the inclusion criteria</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Cevimeline First, Then Pilocarpine</title>
          <description>Cevimeline First then Pilocarpine: Cevimeline (30mg three times a day) for 4 weeks (First intervention period) and then pilocarpine (5 mg three times a day) for 4 weeks (second intervention period). In between first and second intervention period, participants had a washout period for one week.</description>
        </group>
        <group group_id="P2">
          <title>Pilocarpine First, Then Cevimeline</title>
          <description>Pilocarpine First then Cevimeline: Pilocarpine (5 mg three times a day) for 4 weeks (first intervention period) and then Cevimeline (30mg three times a day) for 4 weeks (second intervention period). In between first and second intervention period, participants had a washout period for one week.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>FIRST INTERVENTION: 4 WEEKS</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Washout Period of 1 Week</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>SECOND INTERVENTION: 4 WEEKS</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>All Participants</title>
          <description>Two interventions were assembled:&#xD;
For the first intervention, the SEQUENCE was cevimeline (30mg three times a day) for 4 weeks and then Pilocarpine (5 mg three times a day) for 4 weeks, after the first sequence, the participants had a washout period for one week.&#xD;
For the second intervention, the SEQUENCE was Pilocarpine (5mg three times a day) or 4 weeks and then Cevimeline (30 mg three times a day) for 4 weeks, after the first sequence, the participants had a washout period for one week.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="15"/>
          </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="15"/>
                  </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>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="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </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="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Saliva Production in ml.</title>
        <description>The primary outcome measure was the change of stimulated and non-stimulated saliva in ml from the baseline record.&#xD;
At each appointment (weekly), participants will provide 2 saliva samples to measure their current salivary output. The first measurement will be obtained by having the patient spit as much as he or she could into a cup for five minutes. The amount of saliva in ml will be recorded.&#xD;
The second measurement will be obtained in a similar manner with the addition of having the patient chew on a block of unflavored wax. Patients will complete weekly questionnaires to help determine which side-effects they experience as they take the medications.</description>
        <time_frame>4 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cevimeline</title>
            <description>Cevimeline 30mg administered three times a day in first intervention period or second intervention period for 4 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Pilocarpine</title>
            <description>Pilocarpine 5 mg administered three times a day in either first intervention period or second intervention period</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Saliva Production in ml.</title>
          <description>The primary outcome measure was the change of stimulated and non-stimulated saliva in ml from the baseline record.&#xD;
At each appointment (weekly), participants will provide 2 saliva samples to measure their current salivary output. The first measurement will be obtained by having the patient spit as much as he or she could into a cup for five minutes. The amount of saliva in ml will be recorded.&#xD;
The second measurement will be obtained in a similar manner with the addition of having the patient chew on a block of unflavored wax. Patients will complete weekly questionnaires to help determine which side-effects they experience as they take the medications.</description>
          <units>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="12"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Unstimulated Saliva</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.41" spread="0.5"/>
                    <measurement group_id="O2" value="3.93" spread="0.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Stimulated Saliva</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.31" spread="0.5"/>
                    <measurement group_id="O2" value="10.34" spread="0.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.05</p_value>
            <method>ANOVA</method>
            <method_desc>The p-value is calculated from the ANOVA</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Adverse Events</title>
        <description>Adverse events related to the combination and order of study medication will be measured</description>
        <time_frame>four weeks</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>The adverse events are reported per intervention (4 weeks with each medication)</time_frame>
      <desc>No adverse events were presented in any of the intervention sequences</desc>
      <group_list>
        <group group_id="E1">
          <title>Cevimeline Then Pilocarpine (Intervention 1)</title>
          <description>Cevimeline then pilocarpine One week washout period</description>
        </group>
        <group group_id="E2">
          <title>Pilocarpine Then Cevimeline (Intervention 2)</title>
          <description>Pilocarpine then cevimeline One week washout period</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
              </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>
    <limitations_and_caveats>There are limitations that affected this study. This is a pilot study with a relative low number of patients.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Juan F. Yepes DDS, MD, MPH, MS, DrPH, Associate Professor</name_or_title>
      <organization>Indiana University School of Dentistry</organization>
      <phone>317-944-9601</phone>
      <email>jfyepes@iupui.edu</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/NCT01690052
org study id: 9999
nct id: NCT01690052
lead sponsor: 
has dmc: No
The main objectives were: 1) To determine the efficacy of both cevimeline and pilocarpine in
      the secretion of saliva in patients with xerostomia, and 2) To compare the side-effects
      between the treatment for xerostomia with cevimeline and with pilocarpine.
Pilocarpine is a cholinergic agonist with predominant muscarinic action.As such, it acts at
      muscarinic-cholinergic receptors found throughout the body and promotes fluid secretion. Due
      to this, one of the main side-effects of pilocarpine is an increased amount of sweating.
      Thus, not only are the salivary glands stimulated, but all of the body's exocrine glands'
      production is heightened. On the other hand, cevimeline is a drug with a high affinity for
      specific muscarinic receptors (M3) located on lachrymal and salivary gland epithelium. At
      least in theory, cevimeline will produce less side effects compared with pilocarpine because
      of the higher affinity for the muscarinic receptors located in the salivary glands. A limited
      number of human clinical trials in the efficacy of cevimeline and pilocarpine to increase the
      production of saliva and the side effects have been performed with no conclusive results.

      The main purposes of this study were to determine the efficacy of cevimeline and pilocarpine
      in the secretion of saliva in patients with xerostomia, and to compare the side-effects
      between these two medications.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Change From Baseline in Saliva Production in ml.
time frame: 4 weeks
description: The primary outcome measure was the change of stimulated and non-stimulated saliva in ml from the baseline record.
At each appointment (weekly), participants will provide 2 saliva samples to measure their current salivary output. The first measurement will be obtained by having the patient spit as much as he or she could into a cup for five minutes. The amount of saliva in ml will be recorded.
The second measurement will be obtained in a similar manner with the addition of having the patient chew on a block of unflavored wax. Patients will complete weekly questionnaires to help determine which side-effects they experience as they take the medications.
measure: Adverse Events
time frame: four weeks
description: Adverse events related to the combination and order of study medication will be measured
arm group label: Cevimeline
arm group type: Active Comparator
description: Cevimeline vs Pilocarpine
arm group label: Pilocarpine
arm group type: Active Comparator
description: Pilocarpine vs. Cevimeline
intervention type: Drug
intervention name: Cevimeline
description: Cevimlenine Vs Pilocarpine, cross over design. Two sequences were evaluated "cevimeline first, then pilocarpine" and "pilocarpine first, then cevimeline". Each sequence was evaluated for 4 weeks with one week "washout" period in between both sequences. 15 patients were randomly assigned to a specific sequence by a research pharmacist independent from the study authors. The patients received 30mg of cevimeline three times a day and pilocarpine 5mg three times a day.
arm group label: Cevimeline
intervention type: Drug
intervention name: Pilocarpine
description: Cevimlenine Vs Pilocarpine, cross over design, 4 weeks, one week wash out
arm group label: Pilocarpine
criteria: 
gender: All
minimum age: 21 Years
maximum age: N/A
healthy volunteers: No
last name: Joel Thompson, PhD
role: Principal Investigator
affiliation: University of Kentucky
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Kentucky
investigator full name: Joel Thompson, PhD
investigator title: PRS administrator
mesh term: Xerostomia
mesh term: Pilocarpine
mesh term: Cevimeline
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: There are limitations that affected this study. This is a pilot study with a relative low number of patients.
point of contact: 