Rilpivirine (RPV)

Associated long-acting platforms

Aqueous drug particle suspension, Oral solid form

Administration route

Oral, Intramuscular

Therapeutic area(s)

Use case(s)

Use of drug

Dosage

Drug information

Delivery device(s)

Not provided

Scale-up prospects

Compound is commercially manufactured.

Tentative equipment list for manufacturing

Netzsch ball mill, high pressure homogenizer.

Manufacturing

The manufacturing process for RPV is considered to be non-standard due to the inclusion of an aseptic processing step. RPV is light-sensitive, and exposure to light can induce conversion into a Z-isomer form which can affect pharmacokinetic data and activity. Therefore, all processing, manufacturing and storage stages must implement mitigation procedures and protection from light. The RPV nanosuspension is stored aseptically in single-use glass vials with a protective nitrogen atmosphere. The formulation requires refrigerated storage and is stable for up to three years at 5°C.

Specific analytical instrument required for characterization of formulation

Laser diffractor (determine particle size), FT-IR UHPLC (chemical identification), UHPLC (chromatographic purity), paddle apparatus & UPLC/UV (determine in-vitro drug release for QC / dissolution testing).

HPTN 076

Identifier

NCT02165202

Link

https://clinicaltrials.gov/ct2/show/NCT02165202

Phase

Phase II

Status

Completed

Sponsor

PATH

More details

Not provided

Purpose

Comparing the safety of an intramuscular (IM) injection of TMC278 LA to a placebo given once every eight weeks over a 40 week period among sexually active, HIV- uninfected women.

Interventions

Intervention 1

Intervention 2

Intervention 3

Intervention 4

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2014-10-01

Anticipated Date of Last Follow-up
2018-07-27

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2015-04-13

Actual Completion Date
2017-03-09

Studied populations

Age Cohort

• Adults

Genders

• Cisgender female

Accepts pregnant individuals
No

Accepts lactating individuals
No

Accepts healthy individuals
Yes

Comments about the studied populations

Inclusion Criteria: - Women, 18- 45 years (inclusive) of age at Enrolment. - Female at birth. - Willing and able to provide informed consent to take part in the study, provide adequate locator information and acceptability and adherence assessments throughout the study. - Understands and agrees to local reporting requirements for sexually transmitted infections (STis). - No evidence of an active STI and no diagnosis of Chlamydia trachomatis (CT), Neisseria gonorrhoeae (GC), or syphilis within the last 6 months. - Availability to return for all study visits and participate in all study-related procedures. - Must agree to use condoms for the duration of the study. - Must agree not to participate in other concurrent drug or vaccine trials. - Normal laboratory values.

Health status

Study type

Interventional (clinical trial)

Enrollment

136

Allocation

Randomized

Intervention model

Single group assignment

Intervention model description

Not provided

Masking

Double-blind masking

Masking description

Double (Participant, Investigator)

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

PrEP

Key resources

MWRI-01

Identifier

NCT01656018

Link

https://clinicaltrials.gov/ct2/show/NCT01656018

Phase

Phase I

Status

Completed

Sponsor

Janssen Research & Development, LLC

More details

Not provided

Purpose

Evaluate the safety, acceptability, pharmacokinetics, and ex vivo pharmacodynamics of long-acting TMC278 when administered as an intramuscular injection in HIV-1 negative adults.

Interventions

Intervention 1

Intervention 2

Intervention 3

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2012-11-01

Anticipated Date of Last Follow-up
2016-04-06

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2016-01-01

Actual Completion Date
2016-01-01

Studied populations

Age Cohort

• Adults

Genders

• All

Accepts pregnant individuals
No

Accepts lactating individuals
No

Accepts healthy individuals
Yes

Comments about the studied populations

Inclusion Criteria: - Human immunodeficiency virus type 1 (HIV-1) seronegative at screening and enrolment. - Not pregnant or breastfeeding females. - Agrees to protocol-defined method of contraception. - Abstinence from insertion of anything in rectum (eg, medication, enema, penis, or sex toy) for 72 hours before and 72 hours after each rectal biopsy visit. - Abstinence from insertion of anything in vagina (eg, tampon, medication, douche, penis, or sex toy) for 72 hours before and 72 hours after each cervical and vaginal biopsy visit.

Health status

Study type

Interventional (clinical trial)

Enrollment

4

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Open label

Masking description

None (Open Label)

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

PrEP

Key resources

SSAT 040

Identifier

NCT01275443

Link

https://clinicaltrials.gov/ct2/show/NCT01275443

Phase

Phase I

Status

Completed

Sponsor

St Stephens Aids Trust

More details

Not provided

Purpose

Investigate the levels of the drug (TMC278LA) in the blood, tissues and fluids of the rectum, in addition to the safety and tolerability of the drug when given as a single dose.

Interventions

Intervention 1

Intervention 2

Intervention 3

Intervention 4

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2011-01-01

Anticipated Date of Last Follow-up
2017-06-23

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2012-06-01

Actual Completion Date
2012-06-01

Studied populations

Age Cohort

• Adults

Genders

• All

Accepts pregnant individuals
No

Accepts lactating individuals
No

Accepts healthy individuals
Yes

Comments about the studied populations

Up to 60 evaluable female participants will be enrolled, with more than 40% being of African ancestry. Six male participants will also be enrolled. Female participants will be non-pregnant, non-lactating, aged between 18 to 50 years, and possess a Body Mass Index (BMI) of 16 to 35 kg/m2, inclusive.

Health status

Study type

Interventional (clinical trial)

Enrollment

66

Allocation

Randomized

Intervention model

Single group assignment

Intervention model description

Not provided

Masking

Open label

Masking description

None (Open Label)

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

PrEP

Key resources

CR016747

Identifier

NCT01031589

Link

https://clinicaltrials.gov/ct2/show/NCT01031589

Phase

Phase I

Status

Completed

Sponsor

Tibotec Pharmaceuticals, Ireland

More details

Not provided

Purpose

Investigate the safety/tolerability and pharmacokinetics of a Rilpivirine (RPV; TMC278) long-acting (LA) formulation after single and multiple intramuscular injections.

Interventions

Intervention 1

Intervention 2

Intervention 3

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2010-01-01

Anticipated Date of Last Follow-up
2012-11-19

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2011-07-01

Actual Completion Date
2011-07-01

Studied populations

Age Cohort

• Adults

Genders

• All

Accepts pregnant individuals
No

Accepts lactating individuals
No

Accepts healthy individuals
Yes

Comments about the studied populations

Participants required to be good health. Females were excluded from the trial unless they were postmenopausal for at least 2 years or surgically sterile.

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

19

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Double-blind masking

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

PrEP

Key resources

CR108302

Identifier

NCT03127189

Link

https://clinicaltrials.gov/study/NCT03127189

Phase

Phase I

Status

Completed

Sponsor

Janssen Research & Development, LLC

More details

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.

Purpose

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

Interventions

Intervention 1

Intervention 2

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2017-04-20

Anticipated Date of Last Follow-up
2025-01-31

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2018-04-10

Actual Completion Date
2018-04-10

Studied populations

Age Cohort

• Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
No

Accepts healthy individuals
Yes

Comments about the studied populations

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 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 contraception. - Participant must be non-smoking.

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

110

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Open label

Masking description

None (Open Label)

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Unspecified

Key resources

Proprietary excipients used

No proprietary excipient used

Novel excipients or existing excipients at a concentration above Inactive Ingredients Database (IID) for the specified route of administration

The novel excipient poloxamer 338 (P338) is used in the final G001 clinical formulation. Following both an in-vitro mammalian chromosome aberration and an Ames test, it was considered to be non-genotoxic with no evidence for mutagenicity. Further P338 fertility, genotoxicity and development studies have been conducted with no negative effects, in addition to a 6-week and 9-month minipig repeat-dose toxicity study. No adverse local or systemic toxicity was reported in the minipigs at 100mg/month (Margin of Exposure:19).

Residual solvents used

No residual solvent used

There are either no relevant patents or these were not yet submitted to LAPaL

Publications

There are no publication

Additional documents

No documents were uploaded

Useful links

• Metabolism of Long-Acting Rilpivirine After Intramuscular Injection: HIV Prevention Trials Network Study 076 (HPTN 076)

• Acceptability of a long-acting injectable HIV prevention product among US and African women: findings from a phase 2 clinical Trial (HPTN 076)

• Long-acting rilpivirine as potential pre-exposure prophylaxis for HIV-1 prevention (the MWRI-01 study): an open-label, phase 1, compartmental, pharmacokinetic and pharmacodynamic assessment

• A compartmental pharmacokinetic evaluation of long-acting rilpivirine in HIV-negative volunteers for pre-exposure prophylaxis

• Safety, tolerability and pharmacokinetics of rilpivirine following administration of a long-acting formulation in healthy volunteers