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

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: TMC278, Long acting (LA)

Study type: Interventional

Funder types: Industry

Identifiers

NCT01656018

CR100803

TMC278-MWRI-01 (Other Identifier)

Details and patient eligibility

About

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).

Full 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.

Enrollment: 4 patients

Sex: All

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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4 participants in 10 patient groups

Arm 1A

Experimental group

Description:

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

Treatment:

Drug: TMC278, Long acting (LA)

Arm 1B

Experimental group

Description:

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

Treatment:

Drug: TMC278, Long acting (LA)

Arm 2A

Experimental group

Description:

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

Treatment:

Drug: TMC278, Long acting (LA)

Arm 2B

Experimental group

Description:

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

Treatment:

Drug: TMC278, Long acting (LA)

Arm 3A

Experimental group

Description:

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

Treatment:

Drug: TMC278, Long acting (LA)

Arm 3B

Experimental group

Description:

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

Treatment:

Drug: TMC278, Long acting (LA)

Arm 4A

Experimental group

Description:

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.

Treatment:

Drug: TMC278, Long acting (LA)

Arm 4B

Experimental group

Description:

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.

Treatment:

Drug: TMC278, Long acting (LA)

Arm 5A

Experimental group

Description:

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.

Treatment:

Drug: TMC278, Long acting (LA)

Arm 5B

Experimental group

Description:

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.

Treatment:

Drug: TMC278, Long acting (LA)