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

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)

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: TMC278 (Rilpivirine) LA; Placebo

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
• Enrollment (Actual): 19
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 58 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Rate and extent of absorption of TMC278 following single or three successive IM injections	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

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

Collaborators and Investigators

• Sponsor: Tibotec Pharmaceuticals, Ireland

Publications and helpful links

General Publications

• Verloes R, Deleu S, Niemeijer N, Crauwels H, Meyvisch P, Williams P. Safety, tolerability and pharmacokinetics of rilpivirine following administration of a long-acting formulation in healthy volunteers. HIV Med. 2015 Sep;16(8):477-84. doi: 10.1111/hiv.12247. Epub 2015 May 18.

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): July 1, 2011
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: December 10, 2009
• First Submitted That Met QC Criteria: December 10, 2009
• First Posted (Estimate): December 14, 2009

Study Record Updates

• Last Update Posted (Estimate): November 20, 2012
• Last Update Submitted That Met QC Criteria: November 19, 2012
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Keywords: HIV Seronegativity; HIV; TMC278; Non-nucleoside reverse transcriptase inhibitor; TMC278-TiDP15-C158; TMC278-C158
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Rilpivirine
• Other Study ID Numbers: CR016747