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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Janssen Research & Development, LLC
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01656018
First received: July 31, 2012
Last updated: July 14, 2014
Last verified: July 2014
  Purpose

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).


Condition Intervention Phase
Healthy
Drug: TMC278, Long acting (LA)
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:
  • Number of participants with adverse events [ Time Frame: Up to 280 days ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • TMC278 concentration in plasma [ Time Frame: Up to 280 days ] [ Designated as safety issue: No ]
  • TMC278 concentration in endocervical fluid [ Time Frame: Up to 280 days ] [ Designated as safety issue: No ]
  • TMC278 concentration in vaginal fluid [ Time Frame: Up to 280 days ] [ Designated as safety issue: No ]
  • TMC278 concentration in rectal fluid [ Time Frame: Up to 280 days ] [ Designated as safety issue: No ]
  • TMC278 concentration in cervical tissue [ Time Frame: Up to 280 days ] [ Designated as safety issue: No ]
  • TMC278 concentration in vaginal tissue [ Time Frame: Up to 280 days ] [ Designated as safety issue: No ]
  • TMC278 concentration in rectal tissue [ Time Frame: Up to 280 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 90
Study Start Date: November 2012
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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
Experimental: Arm 1B
Male participants will receive a single dose of long acting TMC278 1200 mg IM at baseline in Arm 1B.
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
Experimental: Arm 2A
Female participants will receive a single dose of long acting TMC278 600 mg IM at baseline in Arm 2A.
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
Experimental: Arm 2B
Male participants will receive a single dose of long acting TMC278 600 mg IM at baseline in Arm 2B.
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
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.
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
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.
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
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.
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
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.
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
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.
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
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.
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

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

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01656018

Contacts
Contact: Use link at the bottom of the page to see if you qualify for an enrolling site (see list). If you still have questions: JNJ.CT@sylogent.com

Locations
United States, Pennsylvania
Recruiting
Pittsburgh, Pennsylvania, United States
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research and Development, LLC Clinical Trial Janssen Research and Development LLC
  More Information

Additional Information:
No publications provided

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01656018     History of Changes
Other Study ID Numbers: CR100803, TMC278-MWRI-01
Study First Received: July 31, 2012
Last Updated: July 14, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Janssen Research & Development, LLC:
Healthy
TMC278
Human Immunodeficiency Virus Type 1
HIV-1
Pharmacokinetics
Ex-vivo pharmacodynamics

ClinicalTrials.gov processed this record on July 26, 2014