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A Study to Evaluate Safety, Acceptability, Pharmacokinetics, and ex Vivo Pharmacodynamics of TMC278 Long Acting Formulation in HIV-1 Seronegative Participants

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ClinicalTrials.gov Identifier: NCT01656018
Recruitment Status : Completed
First Posted : August 2, 2012
Last Update Posted : April 7, 2016
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Tracking Information
First Submitted Date  ICMJE July 31, 2012
First Posted Date  ICMJE August 2, 2012
Last Update Posted Date April 7, 2016
Study Start Date  ICMJE November 2012
Actual Primary Completion Date January 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 10, 2012)
  • Number of participants with adverse events [ Time Frame: Up to 280 days ]
  • Number of participants who would consider using long acting TMC278 for Human immunodeficiency virus (HIV) prevention in the future [ Time Frame: Up to 280 days ]
Original Primary Outcome Measures  ICMJE
 (submitted: July 31, 2012)
  • Number of participants with adverse events [ Time Frame: Up to 280 days ]
    Grade 2 or higher clinical and laboratory adverse events (as defined by the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events) will be evaluated.
  • The number of participants who would consider using long acting TMC278 for Human immunodeficiency virus (HIV) prevention in the future [ Time Frame: up to 252 Days ]
    The number of participants who would consider using long acting TMC278 for HIV prevention in the future will be evaluated.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 10, 2012)
  • TMC278 concentration in plasma [ Time Frame: Up to 280 days ]
  • TMC278 concentration in endocervical fluid [ Time Frame: Up to 280 days ]
  • TMC278 concentration in vaginal fluid [ Time Frame: Up to 280 days ]
  • TMC278 concentration in rectal fluid [ Time Frame: Up to 280 days ]
  • TMC278 concentration in cervical tissue [ Time Frame: Up to 280 days ]
  • TMC278 concentration in vaginal tissue [ Time Frame: Up to 280 days ]
  • TMC278 concentration in rectal tissue [ Time Frame: Up to 280 days ]
Original Secondary Outcome Measures  ICMJE
 (submitted: July 31, 2012)
Determination of the TMC278 concentration in plasma, endocervical fluid, vaginal fluid, rectal fluid, cervical tissue, vaginal tissue, and rectal tissue [ Time Frame: up to 252 Days ]
TMC278 concentration in plasma, endocervical fluid, vaginal fluid, rectal fluid, cervical tissue, vaginal tissue, and rectal tissue will be evaluated.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate Safety, Acceptability, Pharmacokinetics, and ex Vivo Pharmacodynamics of TMC278 Long Acting Formulation in HIV-1 Seronegative Participants
Official Title  ICMJE Phase 1 Open Label Safety, Acceptability, Pharmacokinetic and ex Vivo Pharmacodynamic Study of TMC278 Long Acting (LA) Administered Intramuscularly to HIV-1 Seronegative Individuals
Brief Summary The purpose of this study is to evaluate the safety, acceptability, pharmacokinetics (what the body does to the medication), and ex vivo (tested outside the body) pharmacodynamics (what the medication does to the body) of TMC278 long acting (slowly effective after initial dosage and maintaining its effects over a long period of time) when administered as an intramuscular (ie, in to the muscle) injection in adult participants who are seronegative for human immunodeficiency virus type 1 (HIV-1).
Detailed Description This is an open-label (all people know the identity of the intervention), multi-arm (more than one treatment group), dose-ranging study (clinical study where different doses of study medication are tested against each other) to evaluate the safety, acceptability, pharmacokinetics, and ex vivo pharmacodynamics of a single and multiple intramuscular injections of long acting TMC278 to human immunodeficiency virus type 1 (HIV-1) seronegative (having a negative serum reaction) male and female participants. The study consists of 3 phases including screening phase, treatment phase, and the follow up phase (approximately 4 to 6 months after the first dose of study medication). In treatment phase, enrolled participants will be divided in to 2 arms, ie, Arm A (female participants) which will be further divided in to Arm 1A, Arm 2A, Arm 3A, Arm 4A, and Arm 5A with 12 female participants per arm; and Arm B (male participants) which will be further divided in to Arm 1B, Arm 2B, Arm 3B, Arm 4B, and Arm 5B with 6 male participants per arm. Safety evaluations will include assessment of adverse events, clinical laboratory tests, electrocardiogram, physical examination, and vital signs which will be monitored throughout the study. The total duration of study for each participant will be approximately 5 to 7 months.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Healthy
Intervention  ICMJE Drug: TMC278, Long acting (LA)
TMC278 long acting will be administered IM to the participants as follows: a single dose of TMC278 600 mg will be administered at baseline in Arm 2A and Arm 2B; at Months 2 and 4 in Arm 5A and Arm 5B. A single dose of TMC278 900 mg will be administered at Months 2 and 4 in Arm 4A and Arm 4B. A single dose of TMC278 1200 mg will be administered at baseline in Arm 1A, Arm 1B; Arm 3A, Arm 3B, Arm 4A, Arm 4B, Arm 5A and Arm 5B; at Months 2 and 4 in Arm 3A and Arm 3B.
Other Name: TMC278
Study Arms  ICMJE
  • Experimental: Arm 1A
    Female participants will receive a single dose of long acting TMC278 1200 mg intramuscularly (IM) at baseline (Day 0) in Arm 1A.
    Intervention: Drug: TMC278, Long acting (LA)
  • Experimental: Arm 1B
    Male participants will receive a single dose of long acting TMC278 1200 mg IM at baseline in Arm 1B.
    Intervention: Drug: TMC278, Long acting (LA)
  • Experimental: Arm 2A
    Female participants will receive a single dose of long acting TMC278 600 mg IM at baseline in Arm 2A.
    Intervention: Drug: TMC278, Long acting (LA)
  • Experimental: Arm 2B
    Male participants will receive a single dose of long acting TMC278 600 mg IM at baseline in Arm 2B.
    Intervention: Drug: TMC278, Long acting (LA)
  • Experimental: Arm 3A
    Female participants will receive 3 bi-monthly injections of long acting TMC278 1200 mg IM at baseline, Months 2 and 4 in Arm 3A.
    Intervention: Drug: TMC278, Long acting (LA)
  • Experimental: Arm 3B
    Male participants will receive 3 bi-monthly injections of long acting TMC278 1200 mg IM at baseline, Months 2 and 4 in Arm 3B.
    Intervention: Drug: TMC278, Long acting (LA)
  • Experimental: Arm 4A
    Female participants will receive a single dose of long acting TMC278 1200 mg IM at baseline followed by TMC278 900 mg at Months 2 and 4 in Arm 4A.
    Intervention: Drug: TMC278, Long acting (LA)
  • Experimental: Arm 4B
    Male participants will receive a single dose of long acting TMC278 1200 mg IM at baseline followed by TMC278 900 mg at Months 2 and 4 in Arm 4B.
    Intervention: Drug: TMC278, Long acting (LA)
  • Experimental: Arm 5A
    Female participants will receive a single dose of long acting TMC278 1200 mg IM at baseline followed by TMC278 600 mg at Months 2 and 4 in Arm 5A.
    Intervention: Drug: TMC278, Long acting (LA)
  • Experimental: Arm 5B
    Male participants will receive a single dose of long acting TMC278 1200 mg IM at baseline followed by TMC278 600 mg at Months 2 and 4 in Arm 5B.
    Intervention: Drug: TMC278, Long acting (LA)
Publications * McGowan I, Dezzutti CS, Siegel A, Engstrom J, Nikiforov A, Duffill K, Shetler C, Richardson-Harman N, Abebe K, Back D, Else L, Egan D, Khoo S, Egan JE, Stall R, Williams PE, Rehman KK, Adler A, Brand RM, Chen B, Achilles S, Cranston RD. Long-acting rilpivirine as potential pre-exposure prophylaxis for HIV-1 prevention (the MWRI-01 study): an open-label, phase 1, compartmental, pharmacokinetic and pharmacodynamic assessment. Lancet HIV. 2016 Dec;3(12):e569-e578. doi: 10.1016/S2352-3018(16)30113-8. Epub 2016 Sep 16.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 6, 2016)
4
Original Estimated Enrollment  ICMJE
 (submitted: July 31, 2012)
90
Actual Study Completion Date  ICMJE January 2016
Actual Primary Completion Date January 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Human immunodeficiency virus type 1 (HIV-1) seronegative at screening and enrollment
  • Not pregnant or breastfeeding females
  • Agrees to protocol-defined method of contraception
  • Abstinence from insertion of anything in rectum (eg, medication, enema, penis, or sex toy) for 72 hours before and 72 hours after each rectal biopsy visit
  • Abstinence from insertion of anything in vagina (eg, tampon, medication, douche, penis, or sex toy) for 72 hours before and 72 hours after each cervical and vaginal biopsy visit

Exclusion Criteria:

  • Post-exposure prophylaxis for HIV exposure within 6 months prior to screening and known HIV-infected partners
  • Use of systemic immunomodulatory medications within the 4 weeks prior to the enrollment
  • Use of vaginally or rectally administered medications or products (including condoms) containing Nonoxynol-9 (N-9) within the 4 weeks prior to the enrollment
  • Abnormalities of the cervical, vaginal, or colorectal mucosa, or significant symptom(s), which in the opinion of the clinician represents a contraindication to protocol-required biopsies
  • History of recurrent urticaria
  • History of or electrocardiogram demonstrating prolonged QT interval
  • History of significant gastrointestinal bleeding
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 45 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01656018
Other Study ID Numbers  ICMJE CR100803
TMC278-MWRI-01 ( Other Identifier: Janssen Research and Development, LLC )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Janssen Research & Development, LLC
Study Sponsor  ICMJE Janssen Research & Development, LLC
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Janssen Research and Development, LLC Clinical Trial Janssen Research and Development LLC
PRS Account Janssen Research & Development, LLC
Verification Date April 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP