<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/NCT04484337</url>
  </required_header>
  <id_info>
    <org_study_id>212482</org_study_id>
    <nct_id>NCT04484337</nct_id>
  </id_info>
  <brief_title>Study to Evaluate Pharmacokinetic (PK), Safety and Tolerability of Cabotegravir (CAB) 400 Milligrams Per Milliliter (mg/mL) Formulation in Healthy Adult Participants</brief_title>
  <official_title>A Phase 1, Two-part, Double-blind, Active-control, Randomized Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Repeat-Dose Cabotegravir (CAB 400 mg/mL Formulation) Long-Acting Injection Following Subcutaneous or Intramuscular Administration in Healthy Adult Participants</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>ViiV Healthcare</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>ViiV Healthcare</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an active control, randomized study to investigate the safety, tolerability and PK of&#xD;
      repeat dose administration of long-acting CAB 400 mg/mL formulation intramuscular (IM)&#xD;
      (gluteus medius and vastus lateralis) and subcutaneous (SC) (abdominal) injections in healthy&#xD;
      adult participants.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 31, 2020</start_date>
  <completion_date type="Actual">May 5, 2023</completion_date>
  <primary_completion_date type="Actual">May 5, 2023</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>Participants will receive repeat doses of long-acting CAB 400 mg/mL or CAB 200 mg/mL at four-weekly (Q4W) interval in Part 1 and at 12-weekly (Q12W) interval in Part 2.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
    <masking_description>This will be a double-blind (sponsor-unblind) study.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum observed Plasma concentration (Cmax) for cabotegravir (Part 1 Injection 1)</measure>
    <time_frame>Injection 1 Day 1 to Injection 1 Week 4</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmax for cabotegravir (Part 1 Injection 2)</measure>
    <time_frame>Injection 2 Day 1 to Week 52 follow-up</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmax for cabotegravir (Part 2 Injection 1)</measure>
    <time_frame>Injection 1 Day 1 to Injection 1 Week 12</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmax for cabotegravir (Part 2 Injection 2)</measure>
    <time_frame>Injection 2 Day 1 to Week 52 follow-up</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Time of maximum observed plasma concentration (Tmax) for cabotegravir (Part 1 Injection 1)</measure>
    <time_frame>Injection 1 Day 1 to Injection 1 Week 4</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Tmax for cabotegravir (Part 1 Injection 2)</measure>
    <time_frame>Injection 2 Day 1 to Week 52 follow-up</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Tmax for cabotegravir (Part 2 Injection 1)</measure>
    <time_frame>Injection 1 Day 1 to Injection 1 Week 12</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Tmax for cabotegravir (Part 2 Injection 2)</measure>
    <time_frame>Injection 2 Day 1 to Week 52 follow-up</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under the concentration - time curve from time zero to last quantifiable time point (AUC[0-t]) for cabotegravir (Part 1 Injection 1)</measure>
    <time_frame>Injection 1 Day 1 to Injection 1 Week 4</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC(0-t) for cabotegravir (Part 1 Injection 2)</measure>
    <time_frame>Injection 2 Day 1 to Injection 2 Week 4</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC(0-t) for cabotegravir (Part 2 Injection 1)</measure>
    <time_frame>Injection 1 Day 1 to Injection 1 Week 12</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC(0-t) for cabotegravir (Part 2 Injection 2)</measure>
    <time_frame>Injection 2 Day 1 to Injection 2 Week 12</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Trough concentrations (Ctau) for cabotegravir (Part 1 Injection 1)</measure>
    <time_frame>Injection 1 Day 1 to Injection 1 Week 4</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Ctau for cabotegravir (Part 1 Injection 2)</measure>
    <time_frame>Injection 2 Day 1 to Injection 2 Week 4</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Ctau for cabotegravir (Part 2 Injection 1)</measure>
    <time_frame>Injection 1 Day 1 to Injection 1 Week 12</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Ctau for cabotegravir (Part 2 Injection 2)</measure>
    <time_frame>Injection 2 Day 1 to Injection 2 Week 12</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Apparent terminal phase half-life (T1/2) for cabotegravir (Part 1 Injection 2)</measure>
    <time_frame>Injection 2 Week 4 to Week 52 follow-up</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>T1/2 for cabotegravir (Part 2 Injection 2)</measure>
    <time_frame>Injection 2 Week 12 to Week 52 follow-up</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Absorption rate constant (KALA) for cabotegravir (Part 1 Injection 2)</measure>
    <time_frame>Injection 2 Week 4 to Week 52 follow-up</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>KALA for cabotegravir (Part 2 Injection 2)</measure>
    <time_frame>Injection 2 Week 12 to Week 52 follow-up</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Geometric mean ratio of plasma Ctau of CAB for Cohorts 1,2,3,4, 4b &amp; 4h at Week4 (Part 1 Injection 1) compared to historical data of CAB 200 mg/mL IM (gluteus medius) (Week 8 Ctau following first injection at Week 4 in ATLAS [201585]/FLAIR [201584]Study)</measure>
    <time_frame>At Injection 1 Week 4</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Geometric mean ratio of plasma Ctau of CAB for Cohorts 1,2,3,4, 4b at Week 4 (Part 1 Injection 2) compared to historical data of CAB 200 mg/mL IM (gluteus medius) (Week 12 Ctau following first injection at Week 8 in ATLAS [201585]/FLAIR [201584]Study)</measure>
    <time_frame>At Injection 2 Week 4</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Geometric mean ratio of plasma Ctau of CAB for Cohorts 5 and 6 at Week 12(Part 2 Injection 1) compared to historical data of CAB 200 mg/mL IM (gluteus medius) (Week 8 Ctau following first injection at Week 4 in ATLAS [201585]/FLAIR [201584]Study)</measure>
    <time_frame>At Injection 1 Week 12</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Geometric mean ratio of plasma trough concentration (Ctau) of cabotegravir at Week 4 (Part 1 Injection 1) for each pairwise comparison between Cohorts 1, 2, 3, 4, 4b and 4h</measure>
    <time_frame>At Injection 1 Week 4</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Geometric mean ratio of plasma trough concentration (Ctau) of cabotegravir at Week 4 (Part 1 Injection 2) for each pairwise comparison between Cohorts 1, 2, 3, 4 and 4b</measure>
    <time_frame>At Injection 2 Week 4</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Geometric mean ratio of Plasma AUC(0-t) of cabotegravir at Week 4 (Part 1 Injection 1) for each pairwise comparison between Cohorts 1, 2, 3, 4, 4b and 4h</measure>
    <time_frame>At Injection 1 Week 4</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Geometric mean ratio of Plasma Cmax of cabotegravir at Week 4 (Part 1 Injection 2) for each pairwise comparison between Cohorts 1, 2, 3, 4 and 4b</measure>
    <time_frame>At Injection 2 Week 4</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Geometric mean ratio of Plasma Cmax of cabotegravir at Week 4 (Part 1 Injection 1) for each pairwise comparison between Cohorts 1, 2, 3, 4, 4b and 4h</measure>
    <time_frame>At Injection 1 Week 4</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Geometric mean ratio of Plasma AUC(0-t) of cabotegravir at Week 4 (Part 1 Injection 2) for each pairwise comparison between Cohorts 1, 2, 3, 4 and 4b</measure>
    <time_frame>At Injection 2 Week 4</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Parts 1 and 2: Number of participants with adverse events (AEs)</measure>
    <time_frame>Up to 52 weeks follow-up</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with liver biochemistry abnormalities</measure>
    <time_frame>Up to 52 weeks follow-up</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax for cabotegravir following oral 30 mg administration</measure>
    <time_frame>Up to Day 29</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmax for cabotegravir following oral 30 mg administration</measure>
    <time_frame>Up to Day 29</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC(0-t) for cabotegravir following oral 30 mg administration</measure>
    <time_frame>Up to Day 29</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration at 24 hours (C24) for cabotegravir following oral 30 mg administration</measure>
    <time_frame>At 24 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ctau for cabotegravir at Day 29 following oral 30 mg administration</measure>
    <time_frame>Up to Day 29</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax of cabotegravir for cohort 4h</measure>
    <time_frame>Injection 1 Day 1 to Week 52 follow-up</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmax of cabotegravir for cohort 4h</measure>
    <time_frame>Injection 1 Day 1 to Week 52 follow-up</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC(0-t) of cabotegravir for cohort 4h</measure>
    <time_frame>Injection 1 Day 1 to Week 52 follow-up</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ctau of cabotegravir for cohort 4h</measure>
    <time_frame>Injection 1 Day 1 to Week 52 follow-up</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>T1/2 of cabotegravir for cohort 4h</measure>
    <time_frame>Injection 1 Day 1 to Week 52 follow-up</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>KALA of cabotegravir for cohort 4h</measure>
    <time_frame>Injection 1 Day 1 to Week 52 follow-up</time_frame>
  </secondary_outcome>
  <number_of_arms>15</number_of_arms>
  <enrollment type="Actual">138</enrollment>
  <condition>HIV Infections</condition>
  <arm_group>
    <arm_group_label>Part 1:Cohort 1: CAB 400 mg/mL IM gluteal</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1:Cohort 1: CAB 200 mg/mL IM gluteal</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1:Cohort 2: CAB 400 mg/mL SC abdominal</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1:Cohort 2: CAB 200 mg/mL SC abdominal</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1:Cohort 3: CAB 400 mg/mL IM (lateral thigh)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1:Cohort 3: CAB 200 mg/mL IM (lateral thigh)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1: Cohort 4: CAB 400 mg/mL (IM or SC)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1: Cohort 4: CAB 200 mg/mL (IM or SC)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2: Cohort 5: CAB 400 mg/mL IM (gluteus medius)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2: Cohort 5: CAB 200 mg/mL IM (gluteus medius)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2: Cohort 6: CAB 400 mg/mL IM (gluteus medius)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2: Cohort 6: CAB 200 mg/mL IM (gluteus medius)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1: Cohort 4b: CAB 400 mg/mL (SC)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1: Cohort 4h: CAB 400 mg/mL (SC)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1: Cohort 4h: CAB 200 mg/mL (SC)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cabotegravir sodium (Oral Lead In)</intervention_name>
    <description>CAB will be available as 30 mg tablets for oral administration.</description>
    <arm_group_label>Part 1: Cohort 4: CAB 200 mg/mL (IM or SC)</arm_group_label>
    <arm_group_label>Part 1: Cohort 4: CAB 400 mg/mL (IM or SC)</arm_group_label>
    <arm_group_label>Part 1: Cohort 4b: CAB 400 mg/mL (SC)</arm_group_label>
    <arm_group_label>Part 1: Cohort 4h: CAB 200 mg/mL (SC)</arm_group_label>
    <arm_group_label>Part 1: Cohort 4h: CAB 400 mg/mL (SC)</arm_group_label>
    <arm_group_label>Part 1:Cohort 1: CAB 200 mg/mL IM gluteal</arm_group_label>
    <arm_group_label>Part 1:Cohort 1: CAB 400 mg/mL IM gluteal</arm_group_label>
    <arm_group_label>Part 1:Cohort 2: CAB 200 mg/mL SC abdominal</arm_group_label>
    <arm_group_label>Part 1:Cohort 2: CAB 400 mg/mL SC abdominal</arm_group_label>
    <arm_group_label>Part 1:Cohort 3: CAB 200 mg/mL IM (lateral thigh)</arm_group_label>
    <arm_group_label>Part 1:Cohort 3: CAB 400 mg/mL IM (lateral thigh)</arm_group_label>
    <arm_group_label>Part 2: Cohort 5: CAB 200 mg/mL IM (gluteus medius)</arm_group_label>
    <arm_group_label>Part 2: Cohort 5: CAB 400 mg/mL IM (gluteus medius)</arm_group_label>
    <arm_group_label>Part 2: Cohort 6: CAB 200 mg/mL IM (gluteus medius)</arm_group_label>
    <arm_group_label>Part 2: Cohort 6: CAB 400 mg/mL IM (gluteus medius)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cabotegravir 400 mg/mL</intervention_name>
    <description>CAB 400 mg/mL will be available for administration by IM injection or SC Injection.</description>
    <arm_group_label>Part 1: Cohort 4: CAB 400 mg/mL (IM or SC)</arm_group_label>
    <arm_group_label>Part 1: Cohort 4b: CAB 400 mg/mL (SC)</arm_group_label>
    <arm_group_label>Part 1: Cohort 4h: CAB 400 mg/mL (SC)</arm_group_label>
    <arm_group_label>Part 1:Cohort 1: CAB 400 mg/mL IM gluteal</arm_group_label>
    <arm_group_label>Part 1:Cohort 2: CAB 400 mg/mL SC abdominal</arm_group_label>
    <arm_group_label>Part 1:Cohort 3: CAB 400 mg/mL IM (lateral thigh)</arm_group_label>
    <arm_group_label>Part 2: Cohort 5: CAB 400 mg/mL IM (gluteus medius)</arm_group_label>
    <arm_group_label>Part 2: Cohort 6: CAB 400 mg/mL IM (gluteus medius)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cabotegravir 200 mg/mL</intervention_name>
    <description>CAB 200 mg/mL will be available for administration by IM injection or SC Injection.</description>
    <arm_group_label>Part 1: Cohort 4: CAB 200 mg/mL (IM or SC)</arm_group_label>
    <arm_group_label>Part 1: Cohort 4h: CAB 200 mg/mL (SC)</arm_group_label>
    <arm_group_label>Part 1:Cohort 1: CAB 200 mg/mL IM gluteal</arm_group_label>
    <arm_group_label>Part 1:Cohort 2: CAB 200 mg/mL SC abdominal</arm_group_label>
    <arm_group_label>Part 1:Cohort 3: CAB 200 mg/mL IM (lateral thigh)</arm_group_label>
    <arm_group_label>Part 2: Cohort 5: CAB 200 mg/mL IM (gluteus medius)</arm_group_label>
    <arm_group_label>Part 2: Cohort 6: CAB 200 mg/mL IM (gluteus medius)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Topical non-steroidal anti-inflammatory drug</intervention_name>
    <description>Non-steroidal anti-inflammatory drug will be available for topical application</description>
    <arm_group_label>Part 1: Cohort 4b: CAB 400 mg/mL (SC)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Topical steroid</intervention_name>
    <description>Steroid will be available for topical application</description>
    <arm_group_label>Part 1: Cohort 4b: CAB 400 mg/mL (SC)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo creams/gels</intervention_name>
    <description>Placebo creams/gels will be available for topical application</description>
    <arm_group_label>Part 1: Cohort 4b: CAB 400 mg/mL (SC)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Recombinant human hyaluronidase PH20 (rHuPH20)</intervention_name>
    <description>rHuPH20 will be available for administration by SC Injection</description>
    <arm_group_label>Part 1: Cohort 4h: CAB 200 mg/mL (SC)</arm_group_label>
    <arm_group_label>Part 1: Cohort 4h: CAB 400 mg/mL (SC)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participant must be 18 to 50 years of age inclusive, at the time of signing the&#xD;
             informed consent.&#xD;
&#xD;
          -  Participants who are overtly healthy as determined by medical evaluation.&#xD;
&#xD;
          -  A participant with a clinical abnormality or laboratory parameters which is/are not&#xD;
             specifically listed in the inclusion or exclusion criteria, outside the reference&#xD;
             range for the population being studied may be included if the investigator determines&#xD;
             and documents that the finding is unlikely to introduce additional risk factors and&#xD;
             will not interfere with the study procedures.&#xD;
&#xD;
          -  Participants who are negative on two consecutive tests for Severe acute respiratory&#xD;
             syndrome coronavirus 2 (SARS-CoV-2), performed at Screening and within 5 days of&#xD;
             admission to the Phase I unit, using an approved molecular test (Polymerase chain&#xD;
             reaction [PCR]).&#xD;
&#xD;
          -  Body weight more than or equal to (&gt;=)40 kilogram (kg) and body mass index (BMI)&#xD;
             within the range 18 to 32 kilogram per square meter (kg/m^2).&#xD;
&#xD;
          -  Male participants are eligible to participate if they agree to use contraceptive&#xD;
             methods and refrain from donating sperm.&#xD;
&#xD;
          -  A female participant is eligible to participate if she is not pregnant or&#xD;
             breastfeeding, and at least one of the following conditions applies: Is not a woman of&#xD;
             childbearing potential (WOCBP) or is a WOCBP and using a contraceptive method that is&#xD;
             highly effective, with a failure rate of less than (&lt;)1 percent(%).&#xD;
&#xD;
          -  Capable of giving signed informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Signs and symptoms which in the opinion of the investigator are suggestive of&#xD;
             Coronavirus disease 2019 (COVID-19) (that is [i.e.] fever, cough etc) within 14 days&#xD;
             of inpatient admission.&#xD;
&#xD;
          -  Contact with known COVID-19 positive person/s in the 14 days prior to inpatient&#xD;
             admission.&#xD;
&#xD;
          -  History or presence of/significant history of or current cardiovascular, respiratory,&#xD;
             hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders&#xD;
             capable of significantly altering the absorption, metabolism, or elimination of drugs;&#xD;
             constituting a risk when taking the study intervention or interfering with the&#xD;
             interpretation of data.&#xD;
&#xD;
          -  Abnormal blood pressure as determined by the investigator.&#xD;
&#xD;
          -  Alanine transaminase (ALT) more than (&gt;)1.5 times upper limit of normal (ULN).&#xD;
&#xD;
          -  Bilirubin &gt;1.5 times ULN (isolated bilirubin &gt;1.5 times ULN is acceptable if bilirubin&#xD;
             is fractionated and direct bilirubin &lt;35%).&#xD;
&#xD;
          -  Current or chronic history of liver disease, or known hepatic or biliary abnormalities&#xD;
             (with the exception of Gilbert's syndrome or asymptomatic gallstones).&#xD;
&#xD;
          -  Corrected QT interval (QTc) &gt;450 milliseconds (msec).&#xD;
&#xD;
          -  A known hypersensitivity to hyaluronidases (Cohort 4h only).&#xD;
&#xD;
          -  The participant has an underlying skin disease or disorder (infection, inflammation,&#xD;
             dermatitis, eczema, drug rash, drug allergy, psoriasis, food allergy, urticaria) that&#xD;
             would interfere with assessment of injection sites.&#xD;
&#xD;
          -  Current or anticipated need for chronic anti-coagulation with the exception of the use&#xD;
             of low dose acetylsalicylic acid (less than or equal to [&lt;=]325 mg) or hereditary&#xD;
             coagulation and platelet disorders such as hemophilia or Von Willebrand Disease.&#xD;
&#xD;
          -  Participants considered to have insufficient musculature to allow safe administration&#xD;
             of CAB 400 mg/mL (gluteus medius or vastus lateralis).&#xD;
&#xD;
          -  History of ongoing or clinically relevant seizure disorder within the previous 2&#xD;
             years, including participants who have required treatment for seizures within this&#xD;
             time period.&#xD;
&#xD;
          -  History of or on-going high-risk behaviors that may put the participant at increased&#xD;
             risk for Human Immunodeficiency Virus (HIV) acquisition in the opinion of the&#xD;
             investigator. This includes participants in HIV discordant relationships, or men who&#xD;
             report current or prior unprotected anal sex with other men and those reporting prior&#xD;
             or current injecting drug use.&#xD;
&#xD;
          -  Participation in another concurrent clinical study or prior clinical study (with the&#xD;
             exception of imaging trials) prior to the first dosing day in the current study: 30&#xD;
             days, 5 half-lives or twice the duration of the biological effect of the&#xD;
             investigational product (whichever is longer).&#xD;
&#xD;
          -  Participation in the study would result in loss of blood or blood products in excess&#xD;
             of 500 mL within 56 days.&#xD;
&#xD;
          -  The participant has participated in a clinical trial and has received an&#xD;
             investigational product within the following time period prior to the first dosing day&#xD;
             in the current study: 30 days, 5 half-lives or twice the duration of the biological&#xD;
             effect of the investigational product (whichever is longer).&#xD;
&#xD;
          -  Exposure to more than four new chemical entities within 12 months prior to the first&#xD;
             dosing day.&#xD;
&#xD;
          -  Presence of hepatitis B surface antigen (HBsAg), or positive hepatitis C antibody test&#xD;
             result at screening or within 3 months prior to first dose of study treatment.&#xD;
&#xD;
          -  A positive pre-study drug/alcohol screen.&#xD;
&#xD;
          -  Exclusion criteria for screening electrocardiogram (ECG):&#xD;
&#xD;
               1. Heart rate: For Males &lt;45 or &gt;100 beats per minute (bpm), for females &lt;50 or &gt;100&#xD;
                  bpm.&#xD;
&#xD;
               2. PR Interval: For males and females &lt;120 or &gt;220 msec.&#xD;
&#xD;
               3. QRS duration: For males and females &lt;70 or &gt;120 msec.&#xD;
&#xD;
               4. QT duration corrected for heart rate by Fridericia's formula (QTcF) interval: For&#xD;
                  males and females &gt;450 msec.&#xD;
&#xD;
          -  Evidence of previous myocardial infarction.&#xD;
&#xD;
          -  Any conduction abnormality (including but not specific to left or right complete&#xD;
             bundle branch block, atrioventricular [AV] block [2nd degree or higher],&#xD;
             Wolff-Parkinson-White [WPW] syndrome).&#xD;
&#xD;
          -  Sinus Pauses &gt;3 seconds.&#xD;
&#xD;
          -  Any significant arrhythmia which, in the opinion of the Investigator or&#xD;
             GlaxoSmithKline (GSK)/ViiV Medical monitor, will interfere with the safety for the&#xD;
             individual participant.&#xD;
&#xD;
          -  Non-sustained or sustained ventricular tachycardia (&gt;=3 consecutive ventricular&#xD;
             ectopic beats).&#xD;
&#xD;
          -  Positive HIV antibody/antigen test. Participants will be advised regarding safer sex.&#xD;
             In the event a participant acquires HIV during the course of the study they will be&#xD;
             required to withdraw from the study and will be referred urgently to an HIV treatment&#xD;
             center for further management.&#xD;
&#xD;
          -  Regular use of known drugs of abuse.&#xD;
&#xD;
          -  Regular use of tobacco- or nicotine-containing products within 3 months prior to&#xD;
             screening.&#xD;
&#xD;
          -  History of sensitivity to any of the study medications, or components thereof or a&#xD;
             history of drug or other allergy.&#xD;
&#xD;
          -  Participants with a history of intolerance to or with contraindications to the use of&#xD;
             topical non-steroidal anti-inflammatory drugs (NSAIDs) or topical steroids will be&#xD;
             excluded from participation in Cohort 4b.&#xD;
&#xD;
          -  Regular alcohol consumption within 6 months prior to the study defined as: An average&#xD;
             weekly intake of &gt;14 units for males or &gt;7 units for females.&#xD;
&#xD;
          -  Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or&#xD;
             nicotine-containing products (e.g. nicotine patches or vaporizing devices) within 6&#xD;
             months prior to screening.&#xD;
&#xD;
          -  The participant has a tattoo or other dermatological condition overlying the location&#xD;
             of injection or a prior history of silicone implants (gluteal) which may interfere&#xD;
             with interpretation of injection site reactions or administration of CAB LA.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>GSK Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>ViiV Healthcare</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89113</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Berlin</city>
        <state>New Jersey</state>
        <zip>08009</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78744</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Auckland</city>
        <zip>1010</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>New Zealand</country>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>July 20, 2020</study_first_submitted>
  <study_first_submitted_qc>July 20, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 23, 2020</study_first_posted>
  <last_update_submitted>May 23, 2023</last_update_submitted>
  <last_update_submitted_qc>May 23, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 24, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Cabotegravir</keyword>
  <keyword>Long-Acting Injection</keyword>
  <keyword>Pharmacokinetics</keyword>
  <keyword>Safety</keyword>
  <keyword>Tolerability</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>HIV Infections</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cabotegravir</mesh_term>
    <mesh_term>Anti-Inflammatory Agents</mesh_term>
    <mesh_term>Anti-Inflammatory Agents, Non-Steroidal</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>IPD for this study will be made available via the Clinical Study Data Request site.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.</ipd_time_frame>
    <ipd_access_criteria>Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.</ipd_access_criteria>
    <ipd_url>http://clinicalstudydatarequest.com</ipd_url>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT04484337
org study id: 212482
nct id: NCT04484337
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is an active control, randomized study to investigate the safety, tolerability and PK of
      repeat dose administration of long-acting CAB 400 mg/mL formulation intramuscular (IM)
      (gluteus medius and vastus lateralis) and subcutaneous (SC) (abdominal) injections in healthy
      adult participants.
allocation: Randomized
intervention model: Sequential Assignment
intervention model description: Participants will receive repeat doses of long-acting CAB 400 mg/mL or CAB 200 mg/mL at four-weekly (Q4W) interval in Part 1 and at 12-weekly (Q12W) interval in Part 2.
primary purpose: Treatment
masking: Double (Participant, Investigator)
masking description: This will be a double-blind (sponsor-unblind) study.
measure: Maximum observed Plasma concentration (Cmax) for cabotegravir (Part 1 Injection 1)
time frame: Injection 1 Day 1 to Injection 1 Week 4
measure: Cmax for cabotegravir (Part 1 Injection 2)
time frame: Injection 2 Day 1 to Week 52 follow-up
measure: Cmax for cabotegravir (Part 2 Injection 1)
time frame: Injection 1 Day 1 to Injection 1 Week 12
measure: Cmax for cabotegravir (Part 2 Injection 2)
time frame: Injection 2 Day 1 to Week 52 follow-up
measure: Time of maximum observed plasma concentration (Tmax) for cabotegravir (Part 1 Injection 1)
time frame: Injection 1 Day 1 to Injection 1 Week 4
measure: Tmax for cabotegravir (Part 1 Injection 2)
time frame: Injection 2 Day 1 to Week 52 follow-up
measure: Tmax for cabotegravir (Part 2 Injection 1)
time frame: Injection 1 Day 1 to Injection 1 Week 12
measure: Tmax for cabotegravir (Part 2 Injection 2)
time frame: Injection 2 Day 1 to Week 52 follow-up
measure: Area under the concentration - time curve from time zero to last quantifiable time point (AUC[0-t]) for cabotegravir (Part 1 Injection 1)
time frame: Injection 1 Day 1 to Injection 1 Week 4
measure: AUC(0-t) for cabotegravir (Part 1 Injection 2)
time frame: Injection 2 Day 1 to Injection 2 Week 4
measure: AUC(0-t) for cabotegravir (Part 2 Injection 1)
time frame: Injection 1 Day 1 to Injection 1 Week 12
measure: AUC(0-t) for cabotegravir (Part 2 Injection 2)
time frame: Injection 2 Day 1 to Injection 2 Week 12
measure: Trough concentrations (Ctau) for cabotegravir (Part 1 Injection 1)
time frame: Injection 1 Day 1 to Injection 1 Week 4
measure: Ctau for cabotegravir (Part 1 Injection 2)
time frame: Injection 2 Day 1 to Injection 2 Week 4
measure: Ctau for cabotegravir (Part 2 Injection 1)
time frame: Injection 1 Day 1 to Injection 1 Week 12
measure: Ctau for cabotegravir (Part 2 Injection 2)
time frame: Injection 2 Day 1 to Injection 2 Week 12
measure: Apparent terminal phase half-life (T1/2) for cabotegravir (Part 1 Injection 2)
time frame: Injection 2 Week 4 to Week 52 follow-up
measure: T1/2 for cabotegravir (Part 2 Injection 2)
time frame: Injection 2 Week 12 to Week 52 follow-up
measure: Absorption rate constant (KALA) for cabotegravir (Part 1 Injection 2)
time frame: Injection 2 Week 4 to Week 52 follow-up
measure: KALA for cabotegravir (Part 2 Injection 2)
time frame: Injection 2 Week 12 to Week 52 follow-up
measure: Geometric mean ratio of plasma Ctau of CAB for Cohorts 1,2,3,4, 4b & 4h at Week4 (Part 1 Injection 1) compared to historical data of CAB 200 mg/mL IM (gluteus medius) (Week 8 Ctau following first injection at Week 4 in ATLAS [201585]/FLAIR [201584]Study)
time frame: At Injection 1 Week 4
measure: Geometric mean ratio of plasma Ctau of CAB for Cohorts 1,2,3,4, 4b at Week 4 (Part 1 Injection 2) compared to historical data of CAB 200 mg/mL IM (gluteus medius) (Week 12 Ctau following first injection at Week 8 in ATLAS [201585]/FLAIR [201584]Study)
time frame: At Injection 2 Week 4
measure: Geometric mean ratio of plasma Ctau of CAB for Cohorts 5 and 6 at Week 12(Part 2 Injection 1) compared to historical data of CAB 200 mg/mL IM (gluteus medius) (Week 8 Ctau following first injection at Week 4 in ATLAS [201585]/FLAIR [201584]Study)
time frame: At Injection 1 Week 12
measure: Geometric mean ratio of plasma trough concentration (Ctau) of cabotegravir at Week 4 (Part 1 Injection 1) for each pairwise comparison between Cohorts 1, 2, 3, 4, 4b and 4h
time frame: At Injection 1 Week 4
measure: Geometric mean ratio of plasma trough concentration (Ctau) of cabotegravir at Week 4 (Part 1 Injection 2) for each pairwise comparison between Cohorts 1, 2, 3, 4 and 4b
time frame: At Injection 2 Week 4
measure: Geometric mean ratio of Plasma AUC(0-t) of cabotegravir at Week 4 (Part 1 Injection 1) for each pairwise comparison between Cohorts 1, 2, 3, 4, 4b and 4h
time frame: At Injection 1 Week 4
measure: Geometric mean ratio of Plasma Cmax of cabotegravir at Week 4 (Part 1 Injection 2) for each pairwise comparison between Cohorts 1, 2, 3, 4 and 4b
time frame: At Injection 2 Week 4
measure: Geometric mean ratio of Plasma Cmax of cabotegravir at Week 4 (Part 1 Injection 1) for each pairwise comparison between Cohorts 1, 2, 3, 4, 4b and 4h
time frame: At Injection 1 Week 4
measure: Geometric mean ratio of Plasma AUC(0-t) of cabotegravir at Week 4 (Part 1 Injection 2) for each pairwise comparison between Cohorts 1, 2, 3, 4 and 4b
time frame: At Injection 2 Week 4
measure: Parts 1 and 2: Number of participants with adverse events (AEs)
time frame: Up to 52 weeks follow-up
measure: Number of participants with liver biochemistry abnormalities
time frame: Up to 52 weeks follow-up
measure: Cmax for cabotegravir following oral 30 mg administration
time frame: Up to Day 29
measure: Tmax for cabotegravir following oral 30 mg administration
time frame: Up to Day 29
measure: AUC(0-t) for cabotegravir following oral 30 mg administration
time frame: Up to Day 29
measure: Concentration at 24 hours (C24) for cabotegravir following oral 30 mg administration
time frame: At 24 hours
measure: Ctau for cabotegravir at Day 29 following oral 30 mg administration
time frame: Up to Day 29
measure: Cmax of cabotegravir for cohort 4h
time frame: Injection 1 Day 1 to Week 52 follow-up
measure: Tmax of cabotegravir for cohort 4h
time frame: Injection 1 Day 1 to Week 52 follow-up
measure: AUC(0-t) of cabotegravir for cohort 4h
time frame: Injection 1 Day 1 to Week 52 follow-up
measure: Ctau of cabotegravir for cohort 4h
time frame: Injection 1 Day 1 to Week 52 follow-up
measure: T1/2 of cabotegravir for cohort 4h
time frame: Injection 1 Day 1 to Week 52 follow-up
measure: KALA of cabotegravir for cohort 4h
time frame: Injection 1 Day 1 to Week 52 follow-up
arm group label: Part 1:Cohort 1: CAB 400 mg/mL IM gluteal
arm group type: Experimental
arm group label: Part 1:Cohort 1: CAB 200 mg/mL IM gluteal
arm group type: Active Comparator
arm group label: Part 1:Cohort 2: CAB 400 mg/mL SC abdominal
arm group type: Experimental
arm group label: Part 1:Cohort 2: CAB 200 mg/mL SC abdominal
arm group type: Active Comparator
arm group label: Part 1:Cohort 3: CAB 400 mg/mL IM (lateral thigh)
arm group type: Experimental
arm group label: Part 1:Cohort 3: CAB 200 mg/mL IM (lateral thigh)
arm group type: Active Comparator
arm group label: Part 1: Cohort 4: CAB 400 mg/mL (IM or SC)
arm group type: Experimental
arm group label: Part 1: Cohort 4: CAB 200 mg/mL (IM or SC)
arm group type: Active Comparator
arm group label: Part 2: Cohort 5: CAB 400 mg/mL IM (gluteus medius)
arm group type: Experimental
arm group label: Part 2: Cohort 5: CAB 200 mg/mL IM (gluteus medius)
arm group type: Active Comparator
arm group label: Part 2: Cohort 6: CAB 400 mg/mL IM (gluteus medius)
arm group type: Experimental
arm group label: Part 2: Cohort 6: CAB 200 mg/mL IM (gluteus medius)
arm group type: Active Comparator
arm group label: Part 1: Cohort 4b: CAB 400 mg/mL (SC)
arm group type: Experimental
arm group label: Part 1: Cohort 4h: CAB 400 mg/mL (SC)
arm group type: Experimental
arm group label: Part 1: Cohort 4h: CAB 200 mg/mL (SC)
arm group type: Active Comparator
intervention type: Drug
intervention name: Cabotegravir sodium (Oral Lead In)
description: CAB will be available as 30 mg tablets for oral administration.
arm group label: Part 1: Cohort 4: CAB 200 mg/mL (IM or SC)
arm group label: Part 1: Cohort 4: CAB 400 mg/mL (IM or SC)
arm group label: Part 1: Cohort 4b: CAB 400 mg/mL (SC)
arm group label: Part 1: Cohort 4h: CAB 200 mg/mL (SC)
arm group label: Part 1: Cohort 4h: CAB 400 mg/mL (SC)
arm group label: Part 1:Cohort 1: CAB 200 mg/mL IM gluteal
arm group label: Part 1:Cohort 1: CAB 400 mg/mL IM gluteal
arm group label: Part 1:Cohort 2: CAB 200 mg/mL SC abdominal
arm group label: Part 1:Cohort 2: CAB 400 mg/mL SC abdominal
arm group label: Part 1:Cohort 3: CAB 200 mg/mL IM (lateral thigh)
arm group label: Part 1:Cohort 3: CAB 400 mg/mL IM (lateral thigh)
arm group label: Part 2: Cohort 5: CAB 200 mg/mL IM (gluteus medius)
arm group label: Part 2: Cohort 5: CAB 400 mg/mL IM (gluteus medius)
arm group label: Part 2: Cohort 6: CAB 200 mg/mL IM (gluteus medius)
arm group label: Part 2: Cohort 6: CAB 400 mg/mL IM (gluteus medius)
intervention type: Drug
intervention name: Cabotegravir 400 mg/mL
description: CAB 400 mg/mL will be available for administration by IM injection or SC Injection.
arm group label: Part 1: Cohort 4: CAB 400 mg/mL (IM or SC)
arm group label: Part 1: Cohort 4b: CAB 400 mg/mL (SC)
arm group label: Part 1: Cohort 4h: CAB 400 mg/mL (SC)
arm group label: Part 1:Cohort 1: CAB 400 mg/mL IM gluteal
arm group label: Part 1:Cohort 2: CAB 400 mg/mL SC abdominal
arm group label: Part 1:Cohort 3: CAB 400 mg/mL IM (lateral thigh)
arm group label: Part 2: Cohort 5: CAB 400 mg/mL IM (gluteus medius)
arm group label: Part 2: Cohort 6: CAB 400 mg/mL IM (gluteus medius)
intervention type: Drug
intervention name: Cabotegravir 200 mg/mL
description: CAB 200 mg/mL will be available for administration by IM injection or SC Injection.
arm group label: Part 1: Cohort 4: CAB 200 mg/mL (IM or SC)
arm group label: Part 1: Cohort 4h: CAB 200 mg/mL (SC)
arm group label: Part 1:Cohort 1: CAB 200 mg/mL IM gluteal
arm group label: Part 1:Cohort 2: CAB 200 mg/mL SC abdominal
arm group label: Part 1:Cohort 3: CAB 200 mg/mL IM (lateral thigh)
arm group label: Part 2: Cohort 5: CAB 200 mg/mL IM (gluteus medius)
arm group label: Part 2: Cohort 6: CAB 200 mg/mL IM (gluteus medius)
intervention type: Drug
intervention name: Topical non-steroidal anti-inflammatory drug
description: Non-steroidal anti-inflammatory drug will be available for topical application
arm group label: Part 1: Cohort 4b: CAB 400 mg/mL (SC)
intervention type: Drug
intervention name: Topical steroid
description: Steroid will be available for topical application
arm group label: Part 1: Cohort 4b: CAB 400 mg/mL (SC)
intervention type: Drug
intervention name: Placebo creams/gels
description: Placebo creams/gels will be available for topical application
arm group label: Part 1: Cohort 4b: CAB 400 mg/mL (SC)
intervention type: Drug
intervention name: Recombinant human hyaluronidase PH20 (rHuPH20)
description: rHuPH20 will be available for administration by SC Injection
arm group label: Part 1: Cohort 4h: CAB 200 mg/mL (SC)
arm group label: Part 1: Cohort 4h: CAB 400 mg/mL (SC)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: GSK Clinical Trials
role: Study Director
affiliation: ViiV Healthcare
facility: 
facility: 
facility: 
facility: 
facility: 
country: New Zealand
country: United States
responsible party type: Sponsor
mesh term: HIV Infections
mesh term: Cabotegravir
mesh term: Anti-Inflammatory Agents
mesh term: Anti-Inflammatory Agents, Non-Steroidal
sharing ipd: Yes
ipd description: IPD for this study will be made available via the Clinical Study Data Request site.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd time frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
ipd access criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
ipd url: http://clinicalstudydatarequest.com