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

NCT03127189 | Completed Phase 1 FDA Drug

• 2 other identifiers: CR108302TMC278LAHTX1002
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 2

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (5)

• Number of Participants With Adverse Events as a Measure of Safety and Tolerability

  Baseline, up to 9.5 months

• Session 1: Maximum Observed Plasma Concentration (Cmax)

  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)

  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)

  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)

  Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 16, 24, 48, 72, 120 and 168 hours post-dose

Study Arms (5)

Cohort 1-RPV LA: Treatment B

EXPERIMENTAL

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; Drug: Rilpivirine Long-acting Parenteral Formulation

Cohort 1-RPV LA: Treatment D

EXPERIMENTAL

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; Drug: Rilpivirine Long-acting Parenteral Formulation

Cohort 2-RPV LA: Treatment A

EXPERIMENTAL

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; Drug: Rilpivirine Long-acting Parenteral Formulation

Cohort 2-RPV LA: Treatment C

EXPERIMENTAL

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; Drug: Rilpivirine Long-acting Parenteral Formulation

Cohort 2-RPV LA: Treatment E

EXPERIMENTAL

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; Drug: Rilpivirine Long-acting Parenteral Formulation

Interventions

Rilpivirine DRUG

Rilpivirine 25 mg immediate release oral solution.

Cohort 1-RPV LA: Treatment B; Cohort 1-RPV LA: Treatment D; Cohort 2-RPV LA: Treatment A; Cohort 2-RPV LA: Treatment C; Cohort 2-RPV LA: Treatment E

Rilpivirine Long-acting Parenteral Formulation DRUG

RPV LA 600 mg extended-release suspension for IM injection.

Cohort 1-RPV LA: Treatment B; Cohort 1-RPV LA: Treatment D; Cohort 2-RPV LA: Treatment A; Cohort 2-RPV LA: Treatment C; Cohort 2-RPV LA: Treatment E

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (2)

Celerion

Tempe, Arizona, 85283, United States

Location

Celerion

Lincoln, Nebraska, 68502, United States

Location

MeSH Terms

Interventions

Rilpivirine

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2017
• First Posted: April 25, 2017
• Study Start: April 20, 2017
• Primary Completion: April 10, 2018
• Study Completion: April 10, 2018
• Last Updated: February 3, 2025

Record last verified: 2025-01

Locations

US (2)