Clinical trial NCT02561936: Relative Bioavailability of Three Oral Formulations Candidates of Rilpivirine for Potential Pediatric Use Compared to Oral Tablet
Official title: A Phase 1, Open-label, Randomized, 2-panel, 4-way Crossover Study in Healthy Adult Subjects to Assess the Rilpivirine Relative Bioavailability Compared to the 25-mg Oral Tablet and the Food Effect Following Single Dose Administration of Oral Pediatric Formulation Candidates
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Healthy
EUDRANT
Rilpivirine
Lead sponsor: Janssen Sciences Ireland UC
Sponsor class: INDUSTRY
First posted: 2015-09-28
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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).

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: Up to Hour 168
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC [0-last])
timeFrame: Up to Hour 168
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity])
timeFrame: Up to Hour 168
Secondary outcomes:
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax)
timeFrame: Up to Hour 168
measure: Elimination Rate Constant (Lambda[z])
timeFrame: Up to Hour 168
measure: Elimination Half-Life (t1/2)
timeFrame: Up to Hour 168
measure: Number of Participants with Adverse Events
timeFrame: From signing of the informed consent form up to 30 days after last dose of study drug (Day 1)
measure: Number of Participants with Taste Questionnaire Score
timeFrame: 15 minutes after study drug intake in each treatment period in both panels
Other outcomes:
Locations:
city: Antwerp
country: Belgium
Study officials:
affiliation: Janssen Sciences Ireland UC
name: Janssen Sciences Ireland UC Clinical Trial
role: STUDY_DIRECTOR
References: