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

NCT01656018 | Completed Phase 1

• 2 other identifiers: CR100803TMC278-MWRI-01
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

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).

Conditions

Healthy

Keywords

Healthy; TMC278; Human Immunodeficiency Virus Type 1; HIV-1; Pharmacokinetics; Ex-vivo pharmacodynamics

Outcome Measures

Primary Outcomes (2)

• Number of participants with adverse events

  Up to 280 days

• Number of participants who would consider using long acting TMC278 for Human immunodeficiency virus (HIV) prevention in the future

  Up to 280 days

Secondary Outcomes (7)

• TMC278 concentration in plasma

  Up to 280 days

• TMC278 concentration in endocervical fluid

  Up to 280 days

• TMC278 concentration in vaginal fluid

  Up to 280 days

• TMC278 concentration in rectal fluid

  Up to 280 days

• TMC278 concentration in cervical tissue

  Up to 280 days

Study Arms (10)

Arm 1A

EXPERIMENTAL

Female participants will receive a single dose of long acting TMC278 1200 mg intramuscularly (IM) at baseline (Day 0) in Arm 1A.

Drug: TMC278, Long acting (LA)

Arm 1B

EXPERIMENTAL

Male participants will receive a single dose of long acting TMC278 1200 mg IM at baseline in Arm 1B.

Drug: TMC278, Long acting (LA)

Arm 2A

EXPERIMENTAL

Female participants will receive a single dose of long acting TMC278 600 mg IM at baseline in Arm 2A.

Drug: TMC278, Long acting (LA)

Arm 2B

EXPERIMENTAL

Male participants will receive a single dose of long acting TMC278 600 mg IM at baseline in Arm 2B.

Drug: TMC278, Long acting (LA)

Arm 3A

EXPERIMENTAL

Female participants will receive 3 bi-monthly injections of long acting TMC278 1200 mg IM at baseline, Months 2 and 4 in Arm 3A.

Drug: TMC278, Long acting (LA)

Arm 3B

EXPERIMENTAL

Male participants will receive 3 bi-monthly injections of long acting TMC278 1200 mg IM at baseline, Months 2 and 4 in Arm 3B.

Drug: TMC278, Long acting (LA)

Arm 4A

EXPERIMENTAL

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.

Drug: TMC278, Long acting (LA)

Arm 4B

EXPERIMENTAL

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.

Drug: TMC278, Long acting (LA)

Arm 5A

EXPERIMENTAL

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.

Drug: TMC278, Long acting (LA)

Arm 5B

EXPERIMENTAL

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.

Drug: TMC278, Long acting (LA)

Interventions

TMC278, Long acting (LA) DRUG

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.

Also known as: TMC278

Arm 1A; Arm 1B; Arm 2A; Arm 2B; Arm 3A; Arm 3B; Arm 4A; Arm 4B; Arm 5A; Arm 5B

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (1)

Unknown Facility

Pittsburgh, Pennsylvania, United States

Location

Related Publications (1)

• 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.

  PMID: 27658864 DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

Rilpivirine

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Janssen Research and Development, LLC Clinical Trial

  Janssen Research and Development LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 31, 2012
• First Posted: August 2, 2012
• Study Start: November 1, 2012
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2016
• Last Updated: April 7, 2016

Record last verified: 2016-04

Locations

US (1)