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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Rilpivirine; Drug: Rilpivirine Long-acting Parenteral Formulation

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.

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tempe, Arizona, United States, 85283
      • Celerion
  • Nebraska
    • Lincoln, Nebraska, United States, 68502
      • Celerion

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1-RPV LA: Treatment B; Participants will receive single dose of 25 milligram (mg) rilpivirine (RPV) as an oral solution on Day 1 in Session 1 and Treatment B containing a single intramuscular (IM) injection of 600 mg rilpivirine long-acting parenteral formulation (RPV LA) [with different particle size distribution (PSD) as compared to Treatment A, D, C and E] on Day 1 of session 2. Both the sessions are separated by a wash-out Period of at least 14 days.	Drug: Rilpivirine; Rilpivirine 25 mg immediate release oral solution.; Drug: Rilpivirine Long-acting Parenteral Formulation; RPV LA 600 mg extended-release suspension for IM injection.
Experimental: Cohort 1-RPV LA: Treatment D; Participants will receive single dose of 25 mg rilpivirine (RPV) as an oral solution on Day 1 in Session 1 and Treatment D containing a single IM injection of 600 mg RPV LA [with different PSD as compared to Treatment A, B, C and E) on Day 1 of session 2. Both the sessions are separated by a wash-out Period of at least 14 days.	Drug: Rilpivirine; Rilpivirine 25 mg immediate release oral solution.; Drug: Rilpivirine Long-acting Parenteral Formulation; RPV LA 600 mg extended-release suspension for IM injection.
Experimental: Cohort 2-RPV LA: Treatment A; Participants will receive single dose of 25 mg rilpivirine (RPV) as an oral solution on Day 1 in Session 1 and Treatment A containing a single IM injection of 600 mg RPV LA [with different PSD as compared to Treatment B, C, D and E] on Day 1 of session 2. Both the sessions are separated by a wash-out Period of at least 14 days.	Drug: Rilpivirine; Rilpivirine 25 mg immediate release oral solution.; Drug: Rilpivirine Long-acting Parenteral Formulation; RPV LA 600 mg extended-release suspension for IM injection.
Experimental: Cohort 2-RPV LA: Treatment C; Participants will receive single dose of 25 mg rilpivirine (RPV) as an oral solution on Day 1 in Session 1 and Treatment C containing a single IM injection of 600 mg RPV LA [with different PSD as compared to Treatment A, B, D and E] on Day 1 of session 2. Both the sessions are separated by a wash-out Period of at least 14 days.	Drug: Rilpivirine; Rilpivirine 25 mg immediate release oral solution.; Drug: Rilpivirine Long-acting Parenteral Formulation; RPV LA 600 mg extended-release suspension for IM injection.
Experimental: Cohort 2-RPV LA: Treatment E; Participants will receive single dose of 25 mg rilpivirine (RPV) as an oral solution on Day 1 in Session 1 and Treatment E containing a single IM injection of 600 mg RPV LA [with different PSD as compared to Treatment A, B, C and D] on Day 1 of session 2. Both the sessions are separated by a wash-out Period of at least 14 days.	Drug: Rilpivirine; Rilpivirine 25 mg immediate release oral solution.; Drug: Rilpivirine Long-acting Parenteral Formulation; RPV LA 600 mg extended-release suspension for IM injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Session 2: Maximum Observed Plasma Concentration (Cmax)	The Cmax is the maximum observed plasma concentration.	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
Session 2: Area Under the Plasma Concentration-Time Curve From Time Zero (Day 1) to Day 28 (AUC[0-d28])	The AUC (0-d28) is the area under the plasma concentration-time curve from time of administration up to Day 28 postdose.	1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 408, and 528 hours post-dose
Session 2: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC [0-last])	The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time.	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
Session 2: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity])	The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z); wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events as a Measure of Safety and Tolerability	An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	Baseline, up to 9.5 months
Session 1: Maximum Observed Plasma Concentration (Cmax)	The Cmax is the maximum observed plasma concentration.	Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 16, 24, 48, 72, 120 and 168 hours post-dose
Session 1: Area Under the Plasma Concentration-Time Curve From Time Zero (Day 1) to Day 28 AUC (0-d28)	The AUC (0-d28) is the area under the plasma concentration time curve from time of administration up to Day 28 postdose.	1, 2, 3, 4, 5, 6, 9, 12, 16, 24, 48, 72, 120, 168, hours post-dose
Session 1: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time AUC (0-last)	The AUC (0-last) is the area under the plasma concentration time curve from time zero to last quantifiable time.	Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 16, 24, 48, 72, 120 and 168 hours post-dose
Session 1: Area Under the Plasma Concentration-Time Curve From Time Zero To Infinite Time AUC (0-infinity)	The AUC (0-infinity) is the area under the plasma concentration time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z). wherein AUC(last) is area under the plasma concentration time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.	Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 16, 24, 48, 72, 120 and 168 hours post-dose

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): April 20, 2017
• Primary Completion (Actual): April 10, 2018
• Study Completion (Actual): April 10, 2018

Study Registration Dates

• First Submitted: March 15, 2017
• First Submitted That Met QC Criteria: April 24, 2017
• First Posted (Actual): April 25, 2017

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 31, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Anti-Infective Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Nucleic Acid Synthesis Inhibitors; Antiviral Agents; Reverse Transcriptase Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Rilpivirine
• Other Study ID Numbers: CR108302; TMC278LAHTX1002 (Other Identifier: Janssen Research & Development, LLC)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No