TMC278-TiDP15-C158 - A Study to Examine the Safety, Tolerability and Pharmacokinetics of a Single Dose or Three Successive Doses of Intramuscularly (IM) Injected Long Acting Formulation of TMC278

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01031589
Recruitment Status : Completed
First Posted : December 14, 2009
Last Update Posted : November 20, 2012
Information provided by (Responsible Party):
Tibotec Pharmaceuticals, Ireland

Brief Summary:
The purpose of this study is to examine the safety, local tolerability and pharmacokinetics (how drugs are absorbed in the body, how they are distributed within the body and how they are removed from the body over time) of a single intramuscular injection (injected directly in the muscle) of 300 mg (Panel 1) or 600 mg (Panel 2) of a new long acting form of TMC278. In Panel 3, the safety, local tolerability and pharmacokinetics are being studied after three successive intramuscular injections (single injection on Day1, single injection on Day15 and single injection on Day43) of a selected dose of the same TMC278 LA formulation. The dose of Panel 3 will be determined based on the safety, local tolerability and the pharmacokinetic results obtained in Panel 1 and 2.

Condition or disease Intervention/treatment Phase
HIV Infections Drug: TMC278 (Rilpivirine) LA; Placebo Phase 1

Detailed Description:
This is a Phase I study evaluating the safety, local tolerability and pharmacokinetics (how drugs are absorbed in the body, how they are distributed within the body and how they are removed from the body over time) of a newly selected long acting (LA) formulation of TMC278. This study will enroll 20 healthy volunteers. The first part of the study (Panel 1 + 2) is an open-label study (physician and volunteer know the identity of the drug that is injected) to determine the safety, tolerability and pharmacokinetics of a single IM injection of TMC278 LA. In the first Panel, 300 mg of TMC278 LA is injected once. After 3 days, if no safety or tolerability issues occur, a 600 mg dose of TMC278 LA is injected once in volunteers of Panel 2. The second part of the study is a double blind, placebo-controlled (neither physician nor the volunteer knows who is injected with TMC278 LA or placebo). Volunteers of this third Panel will receive 3 doses (one dose at Day 1, Day 15 and Day 43) of the same LA formulation of TMC278 as used in Panel 1 and 2. The Panel 3 dose will be selected based on the safety, tolerability and pharmacokinetic results obtained in Panel 1 and 2, which are being evaluated by a dedicated Data and Safety Review Committee. The dose for the three consecutive injections will be the same. In all Panels, the injections are given into the muscle of the buttock (alternating left and right buttock in Panel 3). Throughout the study, the injection sites will be monitored closely for signs of pain, pain at touch, itching, bruise, redness or other color, induration, swelling and inflammation by medical staff and the participating volunteers. Every Injection Site Reaction (ISR) that occurs will be documented as an adverse event. Additional safety assessments include monitoring of laboratory work including urine samples, vital signs and ECG. Volunteers of Panel 1 and 2 remain in follow-up for minimally 12 weeks after the injection. They are allowed to leave the study on condition that the TMC278 plasma concentration is below 20 ng/mL and that all previously emerged adverse events resolved or stabilized (i.e. according to the investigator and sponsor, the AE does not require further medical follow-up). The same conditions apply for volunteers of Panel 3. In Panel 1 and 2, volunteers receive one single IM dose of 300 mg or 600 mg TMC278 LA. In Panel 3, volunteers receive three IM doses consecutively (Day 1, Day 15 and Day 43) of TMC278 LA. The dose of the 3 injections in Panel 3 is to be determined, based on the safety, local tolerability and pharmacokinetic data of Panel 1 and 2. Six volunteers receive TMC278 LA, 2 receive placebo.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 19 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Primary Purpose: Prevention
Official Title: Study in Healthy Volunteers to Examine the Safety, Tolerability and Plasma Pharmacokinetics of One Intramuscular (IM) Injection of a Novel TMC278 LA Formulation at 2 Different Doses (Open Label), Followed by a Placebo-controlled Part of Multiple IM Injections at a Selected Dose (Double Blind)
Study Start Date : January 2010
Actual Primary Completion Date : July 2011
Actual Study Completion Date : July 2011

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
Drug Information available for: Rilpivirine

Primary Outcome Measures :
  1. Rate and extent of absorption of TMC278 following single or three successive IM injections [ Time Frame: Panel 1 and 2 and after injection 2 and 3 in Panel 3: 672 hours; after injection 1 in panel 3: 336 hours. ]

Secondary Outcome Measures :
  1. Results of Injection Site evaluations [ Time Frame: Daily for the first week in the study, then weekly for minimally the next 12 weeks. ]
  2. Safety Assessments (monitoring AEs, Lab, Vital Signs, ECG parameters) [ Time Frame: Panel 1 and 2: Continuously throughout the 8 study visits; Panel 3: continuously throughout the 14 study visits. ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 58 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • Non-smoker for at least 3 months prior to selection
  • A BMI of 18.0 to 30.0 kg/m2
  • Normal 12-lead electrocardiogram
  • Healthy on the basis of physical examination, clinical laboratory tests, medical history and vital signs

Exclusion Criteria:

  • Female, except if postmenopausal for at least 2 years or surgically sterile
  • positive urine drug test
  • History of clinically relevant skin disease or drug allergy
  • Participation in an investigational drug study or having received a vaccine within 30 days prior to the first injection of TMC278 LA or placebo
  • Previous participation in a study with oral TMC278, TMC125, TMC120 and/or TMC278 LA

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01031589

Sponsors and Collaborators
Tibotec Pharmaceuticals, Ireland
Study Director: Tibotec Pharmaceuticals Clinical Trial Tibotec Pharmaceutical Limited

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Tibotec Pharmaceuticals, Ireland Identifier: NCT01031589     History of Changes
Other Study ID Numbers: CR016747
First Posted: December 14, 2009    Key Record Dates
Last Update Posted: November 20, 2012
Last Verified: November 2012

Keywords provided by Tibotec Pharmaceuticals, Ireland:
Non-nucleoside reverse transcriptase inhibitor
HIV Seronegativity

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Anti-HIV Agents