Clinical trial NCT03127189: A Study to Investigate the Effect of Different Particle Sizes on the Single-dose Pharmacokinetics of Rilpivirine After Intramuscular Injection of a Long-acting Nanosuspension in Healthy Participants
Official title: A Phase 1, Open-label, Randomized, Parallel-group Study in Healthy Subjects to Investigate the Effect of Different Particle Sizes on the Single-dose Pharmacokinetics of Rilpivirine After Intramuscular Injection of a Long-acting Nanosuspension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2017-04-25
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: The main purpose of this study is to characterize the single-dose pharmacokinetics (PK) of rilpivirine (RPV) after intramuscular (IM) injection of rilpivirine long-acting parenteral formulation (RPV LA) nanosuspensions with different particle size distribution (PSD), in healthy adult participants.

Detailed description: This is a phase 1, open-label (all people know the identity of the intervention), randomized (study medication is assigned by chance), parallel-group, sequential study in healthy adult participants to characterize the single-dose pharmacokinetics (PK) of rilpivirine (RPV) after intramuscular (IM) injection of RPV LA nanosuspensions with different particle size distributions (PSD), in healthy adult participants. A total of 110 healthy adult participants will be enrolled in this study. The study will consist of 2 treatment sessions in a fixed sequential order: Session 1- all participants will receive a single oral dose of rilpivirine 25 milligram (mg) as oral immediate release solution on Day 1; Session 2- the participants will be randomized in session 2 on Day 1 in a 1:1:1:1:1 ratio to Treatments A, B, C, D and E. Each treatment group will receive a single 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 9.5 months. Safety will be monitored throughout the study.

Eligibility criteria: Inclusion Criteria:

* Participant must be willing and able to adhere to the prohibitions and restrictions specified in this protocol
* Contraceptive use by men or women should be consistent with local regulations regarding the use of contraceptive methods for participants participating in clinical studies
* A female participant of childbearing potential must have a negative serum beta-human chorionic gonadotropin test at screening and on Day -1 of each session
* For the duration of the study and for at least 6 months after intramuscular (IM) injection of rilpivirine long-acting parenteral formulation (RPV LA) (or 1 month after administration of rilpivirine (RPV) oral solution for participants who discontinue after Session 1), male and female participants must agree to practice effective methods of contraception, and must agree not to donate sperm (males)/eggs (ova, oocytes; for females) for the purposes of assisted reproduction
* Participant must be non-smoking for at least 3 months prior to screening

Exclusion Criteria:

* Female participant who is breastfeeding at screening
* Participant 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 (such as significant diarrhea, gastric stasis, or constipation that in the investigator's opinion could influence drug absorption or bioavailability), endocrine, neurologic, hematologic, rheumatologic, psychiatric, neoplastic, or metabolic disturbances
* Participant has a history of clinically relevant arrhythmias or history of risk factors for Torsade de Pointes (hypokalemia, family history of long QT)
* Participant has clinically relevant, currently active, or underlying gastrointestinal, cardiovascular, nervous system, psychiatric, metabolic, renal, hepatic, respiratory, inflammatory or infectious disease
* Participant has known allergies, hypersensitivity, or intolerance to RPV or its excipients

Primary outcomes:
measure: Session 2: Maximum Observed Plasma Concentration (Cmax)
timeFrame: Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 408, 528, 672, 1344, 2016, 2688, 3360, 4032, 4704, 5376, and 6048 hours post-dose
measure: Session 2: Area Under the Plasma Concentration-Time Curve From Time Zero (Day 1) to Day 28 (AUC[0-d28])
timeFrame: 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 408, and 528 hours post-dose
measure: Session 2: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC [0-last])
timeFrame: Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 408, 528, 672, 1344, 2016, 2688, 3360, 4032, 4704, 5376, and 6048 hours post-dose
measure: Session 2: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity])
timeFrame: Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168,216, 264, 336, 408, 528, 672, 1344, 2016, 2688, 3360, 4032, 4704, 5376, and 6048 hours post-dose
Secondary outcomes:
measure: Number of Participants With Adverse Events as a Measure of Safety and Tolerability
timeFrame: Baseline, up to 9.5 months
measure: Session 1: Maximum Observed Plasma Concentration (Cmax)
timeFrame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 16, 24, 48, 72, 120 and 168 hours post-dose
measure: Session 1: Area Under the Plasma Concentration-Time Curve From Time Zero (Day 1) to Day 28 AUC (0-d28)
timeFrame: 1, 2, 3, 4, 5, 6, 9, 12, 16, 24, 48, 72, 120, 168, hours post-dose
measure: Session 1: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time AUC (0-last)
timeFrame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 16, 24, 48, 72, 120 and 168 hours post-dose
measure: Session 1: Area Under the Plasma Concentration-Time Curve From Time Zero To Infinite Time AUC (0-infinity)
timeFrame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 16, 24, 48, 72, 120 and 168 hours post-dose
Other outcomes:
Locations:
city: Tempe
country: United States
facility: Celerion
state: Arizona
city: Lincoln
country: United States
facility: Celerion
state: Nebraska
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: