Relative Bioavailability of Three Oral Formulations Candidates of Rilpivirine for Potential Pediatric Use Compared to Oral Tablet

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Dietary Supplement: Standardized Breakfast; Drug: Rilpivirine formulation G009-01; Drug: Rilpivirine formulation G007; Drug: Rilpivirine formulation G002; Drug: Rilpivirine Oral Tablet

Study type: Interventional

Funder types: Industry

Identifiers

NCT02561936

2015-002511-14 (EudraCT Number)

CR107783

TMC278IFD1008 (Other Identifier)

Details and patient eligibility

About

The purpose of this study is to compare the rate and extent of absorption of rilpivirine in healthy adult participants following: 1) administration of a single dose of two different oral dispersible tablet formulation candidates and of an oral granules formulation with that following administration of a single dose of the 25-milligram (mg) oral tablet (EDURANT), after a standardized breakfast; 2) administration of a single dose of one selected oral formulation candidate (a dispersible tablet or granules) in different fed conditions (standardized breakfast or yoghurt) and in the fasted state and breakfast and 3) administration of a single dose of one selected oral formulation candidate (a dispersible tablet or granules) dispersed in water or in orange juice, in fed condition (standardized breakfast).

Full description

This is a Phase 1, open-label, randomized, 2-panel, 4-way crossover study in healthy adult participants to assess the relative bioavailability of rilpivirine following single dose administration of oral pediatric formulation candidates (two dispersible tablet formulations and one granules formulation), compared to the commercially available 25-mg tablet (EDURANT) and to assess the effect of food and different food constituents on the oral bioavailability of rilpivirine following single dose administration of one selected formulation candidate. The study will consist of 2 panels: Panel 1 and Panel 2. In each panel, participants will be randomized to receive treatment A, B, C, D and E, F, G, H, respectively. Pharmacokinetic parameters will be evaluated primarily. Safety will be monitored throughout the study.

Enrollment: 32 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Participants must be willing and able to adhere to the prohibitions and restrictions specified in the protocol and study procedures
• 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 and hematology tests and a urinalysis performed at screening. If there are abnormalities, the participant may be included only if the Investigator judges the abnormalities or deviations from normal to be not clinically significant. This determination must be recorded in the participant's source documents and initialed by the Investigator
• Female participant must be either postmenopausal(amenorrhea for at least 2 years and a serum follicle-stimulating hormone [FSH] level greater than or equal to (>) 40 international units per liter (IU/L) [to be confirmed at screening for all postmenopausal women]), OR permanently sterilized (eg, bilateral tubal occlusion [which includes tubal ligation procedures as consistent with local regulations], total hysterectomy, bilateral salpingectomy, bilateral oophorectomy) or otherwise incapable of becoming pregnant, and have a negative serum pregnancy test at screening
• Male participants heterosexually active with a woman of childbearing potential must agree to use two effective contraceptive methods during the study and for at least 90 days after receiving the last dose of study drugs and male participants must agree not to donate sperm during the study and for at least 90 days after receiving the last dose of study drug
• Participants must be non-smoking for at least 3 months prior to Screening

Exclusion criteria

• Female participants who are 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 participants 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
• Participants with current hepatitis B infection (confirmed by hepatitis B surface antigen [HBsAg]) or hepatitis C infection (confirmed by hepatitis C virus [HCV] antibody), or human immunodeficiency syndrome-1 (HIV-1 ) or HIV-2 infection
• Participants with a history of drug or alcohol abuse according to Diagnostic and Statistical Manual of Mental Disorders (5th edition) (DSM-V) criteria within 5 years before screening or positive test result(s) for alcohol and/or drugs of abuse (including barbiturates, opiates, cocaine, amphetamines, methadone, benzodiazepines, methamphetamine, tetrahydrocannabinol, phencyclidine, and tricyclic antidepressants) at Screening
• Participants with a history of clinically relevant skin disease such as, but not limited to, dermatitis, eczema, drug rash, psoriasis, food allergy, or urticaria

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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32 participants in 8 patient groups

Panel 1: Group 1

Experimental group

Description:

Participants will receive Treatment A (25 milligram \[mg\] rilpivirine \[RPV\] formulated as the oral tablet under fed condition \[standardized breakfast\]) followed by Treatment D (25 mg RPV formulated as granules formulation G002 \[10 g of 2.5 mg/g granules, dispersed in water\] under fed \[standardized breakfast\]) followed by Treatment B (25 mg RPV formulated as dispersible tablet formulation G007 \[10\*2.5 mg tablets, dispersed in water\] under fed condition) followed by Treatment C (25 mg RPV formulated as dispersible tablet formulation G009-01 \[10\*2.5 mg tablets, dispersed in water\] under fed condition).

Treatment:

Drug: Rilpivirine formulation G002

Drug: Rilpivirine Oral Tablet

Drug: Rilpivirine formulation G007

Drug: Rilpivirine formulation G009-01

Dietary Supplement: Standardized Breakfast

Panel 1: Group 2

Experimental group

Description:

Participants will receive treatment B followed by treatment A then treatment C followed by treatment D.

Treatment:

Drug: Rilpivirine formulation G002

Drug: Rilpivirine Oral Tablet

Drug: Rilpivirine formulation G007

Drug: Rilpivirine formulation G009-01

Dietary Supplement: Standardized Breakfast

Panel 1: Group 3

Experimental group

Description:

Participants will receive treatment C followed by treatment B then treatment D followed by treatment A.

Treatment:

Drug: Rilpivirine formulation G002

Drug: Rilpivirine Oral Tablet

Drug: Rilpivirine formulation G007

Drug: Rilpivirine formulation G009-01

Dietary Supplement: Standardized Breakfast

Panel 1: Group 4

Experimental group

Description:

Participants will receive treatment D followed by treatment C then treatment A followed by treatment B.

Treatment:

Drug: Rilpivirine formulation G002

Drug: Rilpivirine Oral Tablet

Drug: Rilpivirine formulation G007

Drug: Rilpivirine formulation G009-01

Dietary Supplement: Standardized Breakfast

Panel 2: Group 1

Experimental group

Description:

Participants will receive Treatment E (25 mg RPV formulated as dispersible tablet formulation G007 or G009-01 or as granules formulation G002 \[10\*2.5 mg tablets or 10 g of 2.5 mg/g granules, dispersed in water\] under fed \[standardized breakfast\] condition) followed by Treatment H (25 mg RPV formulated as dispersible tablet formulation G007 or G009-01 or as granules formulation G002 \[10\*2.5 mg tablets or 10 g of 2.5 mg/g granules, dispersed in water\] under fed \[yoghurt\] condition) followed by Treatment F (25 mg RPV formulated as dispersible tablet formulation G007 or G009-01 or as granules formulation G002 \[10\*2.5 mg tablets or 10 g of 2.5 mg/g granules, dispersed in water\] under fasted condition) followed by Treatment G (25 mg RPV formulated as dispersible tablet formulation G007 or G009-01 or as granules formulation G002 \[10\*2.5 mg tablets or 10 g of 2.5 mg/g granules, dispersed in water\] under fed \[standardized breakfast\] condition).

Treatment:

Drug: Rilpivirine formulation G002

Drug: Rilpivirine formulation G007

Drug: Rilpivirine formulation G009-01

Dietary Supplement: Standardized Breakfast

Panel 2: Group 2

Experimental group

Description:

Participants will receive Treatment F followed by Treatment E then Treatment G followed by Treatment H.

Treatment:

Drug: Rilpivirine formulation G002

Drug: Rilpivirine formulation G007

Drug: Rilpivirine formulation G009-01

Dietary Supplement: Standardized Breakfast

Panel 2: Group 3

Experimental group

Description:

Participants will receive Treatment G followed by Treatment F then Treatment H followed by Treatment E.

Treatment:

Drug: Rilpivirine formulation G002

Drug: Rilpivirine formulation G007

Drug: Rilpivirine formulation G009-01

Dietary Supplement: Standardized Breakfast

Panel 2: Group 4

Experimental group

Description:

Participants will receive Treatment H followed by Treatment G then Treatment E followed by Treatment F.

Treatment:

Drug: Rilpivirine formulation G002

Drug: Rilpivirine formulation G007

Drug: Rilpivirine formulation G009-01

Dietary Supplement: Standardized Breakfast