Clinical trial NCT02547870: A Study to Evaluate the Pharmacokinetic Effects of Different Storage Conditions for a Long-Acting Nanosuspension of Rilpivirine on Pharmacokinetics
Official title: A Phase 1 Open-Label, Randomized, Parallel-Group Study in Healthy Subjects to Investigate the Effect of Different Storage Conditions of a Long-Acting Nanosuspension of Rilpivirine on the Single-Dose Plasma Pharmacokinetics of Rilpivirine After Intramuscular Injection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Human Immunodeficiency Virus Type 1
Keywords: Rilpivirine
Healthy participants
Lead sponsor: Janssen Infectious Diseases BVBA
Sponsor class: INDUSTRY
First posted: 2015-09-11
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare the single-dose pharmacokinetics of rilpivirine (RPV) after intramuscular (IM) injection of rilpivirine long-acting parenteral formulation (RPV-LA) and 'aged' RPV-LA, in healthy adult participants.

Detailed description: This is a phase 1 randomized (study medication is assigned by chance), open-label (all people know the identity of the intervention), parallel-group, sequential study in healthy adult participants to investigate the effect of different storage conditions for RPV-LA on the single-dose pharmacokinetics of rilpivirine (RPV) after intramuscular injection. A total of 60 healthy adult participants will be enrolled in this study. The study will consist of 2 treatment sessions in a fixed sequential order : session 1 of up to day 8, all participants will receive a single oral dose of rilpivirine 25 milligram (mg) tablet on day 1, session 2 will consists of 2 treatment groups. The participants will be randomized in session 2 on Day 1 in a 1:1 ratio to Treatments A and B. Each treatment group will receive one IM injection of RPV LA on Day 1 of session 2. Session 1 and 2 will be separated by a washout period of at least 14 days. The total study duration for each participant will be approximately 6.5 months. Safety will be monitored throughout the study.

Eligibility criteria: Inclusion Criteria:

* Each participant must sign an Informed Consent Form (ICF) indicating that he or she understands the purpose of, and procedures required for, the study and are willing to participate in the study
* Participant must be willing and able to adhere to the prohibitions and restrictions specified in this protocol
* Participant must be healthy on the basis of a medical evaluation that reveals the absence of any clinically significant abnormality and includes a physical examination, medical history, vital signs, Electrocardiogram (ECG), and the results of blood biochemistry, hematology and coagulation tests and a urinalysis performed at Screening
* A female participant of childbearing potential must have a negative serum (beta-human chorionic gonadotropin \[beta-hCG\]) at Screening and a negative urine pregnancy test on day 1
* Participant must be non-smoking for at least 3 months prior to selection

Exclusion Criteria:

* Female participant who is breastfeeding at Screening
* Participants with a history of any illness that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the participant or that could prevent, limit or confound the protocol specified assessments. This may include, but is not limited to, renal dysfunction, significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, neoplastic, or metabolic disturbances
* Has known allergies, hypersensitivity, or intolerance to rilpivirine (RPV) or its excipients
* Has a history of drug allergy such as, but not limited to, sulfonamides and penicillins, or drug allergy witnessed in previous studies with experimental drugs
* Having donated or lost more than 1 unit of blood (500 milliliter \[mL\]) within 60 days or more than 1 unit of plasma within 7 days before the first dose of study drug

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: In session1: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 16, 24, 48, 72, 120 and 168 hours post-dose; In session 2: Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168,216, 264, 336, 408, 528, 672, 1344, 2016, 2688, 3360 and 4032 hours post-dose
measure: Area Under the Plasma Concentration-Time Curve From Time Zero (Day 1) to Day 28 (AUC[0-d28])
timeFrame: In session1: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 16, 24, 48, 72, 120 and 168 hours post-dose; In session 2: Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120 and 168 hours post-dose
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC [0-last])
timeFrame: In session1: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 16, 24, 48, 72, 120 and 168 hours post-dose; In session 2: Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168,216, 264, 336, 408, 528, 672, 1344, 2016, 2688, 3360 and 4032 hours post-dose
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity])
timeFrame: In session1: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 16, 24, 48, 72, 120 and 168 hours post-dose; In session 2: Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168,216, 264, 336, 408, 528, 672, 1344, 2016, 2688, 3360 and 4032 hours post-dose
Secondary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: Up to 180 Days
measure: Time to reach the maximum observed plasma concentration (Tmax)
timeFrame: In session1: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 16, 24, 48, 72, 120 and 168 hours post-dose; In session 2: Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168,216, 264, 336, 408, 528, 672, 1344, 2016, 2688, 3360 and 4032 hours post-dose
measure: Elimination Rate Constant (Lambda [z]) of rilpivirine
timeFrame: In session1: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 16, 24, 48, 72, 120 and 168 hours post-dose; In session 2: Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168,216, 264, 336, 408, 528, 672, 1344, 2016, 2688, 3360 and 4032 hours post-dose
measure: Apparent Terminal Half-life (t[1/2]) of rilpivirine
timeFrame: In session1: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 16, 24, 48, 72, 120 and 168 hours post-dose; In session 2: Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168,216, 264, 336, 408, 528, 672, 1344, 2016, 2688, 3360 and 4032 hours post-dose
Other outcomes:
Locations:
city: Antwerp
country: Belgium
Study officials:
affiliation: Janssen Infectious Diseases BVBA
name: Janssen Infectious Diseases BVBA Clinical Trial
role: STUDY_DIRECTOR
References: