Clinical trial NCT01656018: A Study to Evaluate Safety, Acceptability, Pharmacokinetics, and ex Vivo Pharmacodynamics of TMC278 Long Acting Formulation in HIV-1 Seronegative Participants
Official title: Phase 1 Open Label Safety, Acceptability, Pharmacokinetic and ex Vivo Pharmacodynamic Study of TMC278 Long Acting (LA) Administered Intramuscularly to HIV-1 Seronegative Individuals
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Healthy
TMC278
Human Immunodeficiency Virus Type 1
HIV-1
Pharmacokinetics
Ex-vivo pharmacodynamics
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2012-08-02
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of participants with adverse events
timeFrame: Up to 280 days
measure: Number of participants who would consider using long acting TMC278 for Human immunodeficiency virus (HIV) prevention in the future
timeFrame: Up to 280 days
Secondary outcomes:
measure: TMC278 concentration in plasma
timeFrame: Up to 280 days
measure: TMC278 concentration in endocervical fluid
timeFrame: Up to 280 days
measure: TMC278 concentration in vaginal fluid
timeFrame: Up to 280 days
measure: TMC278 concentration in rectal fluid
timeFrame: Up to 280 days
measure: TMC278 concentration in cervical tissue
timeFrame: Up to 280 days
measure: TMC278 concentration in vaginal tissue
timeFrame: Up to 280 days
measure: TMC278 concentration in rectal tissue
timeFrame: Up to 280 days
Other outcomes:
Locations:
city: Pittsburgh
country: United States
state: Pennsylvania
Study officials:
affiliation: Janssen Research and Development LLC
name: Janssen Research and Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: 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.