A Study of Maribavir Pediatric Formulation in Healthy Adult Participants

Healthy Volunteers Clinical Trial

Official title:

A Phase 1, Open-Label, Randomized, Two-Part Study in Healthy Adult Participants to Evaluate the Relative Bioavailability of Maribavir Pediatric Formulation Compared to the Commercial Formulation, as Well as, Food Effect, and Rabeprazole Gastric Acid-Reducing Effect on the Pharmacokinetics of Single-Dose Maribavir Pediatric Formulation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05918822
• Other study ID #: TAK-620-1024
• Status: Completed
• Phase: Phase 1
• Start date: August 10, 2023
• Est. completion date: August 31, 2023

Study information

• Verified date: September 2023
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study will have 2 parts, Part 1 and Part 2. Participants will only participate in one part.

The main aim of Part 1 of this study is to check the ability of a single dose of maribavir pediatric formulation to be absorbed in the digestive tract compared to commercial tablet formulation and to check how a high-fat, high-calorie meal affects absorption, distribution, and elimination of maribavir pediatric formulation given orally as water suspension.

The main aim of Part 2 of this study is to assess the stomach acid reducing effect of multiple doses of rabeprazole on absorption, distribution, and elimination of maribavir pediatric formulation given orally as water suspension.

Each participant will stay in the study clinic from the day before the first treatment until the day after the last treatment.

Description:

Part 1 is a crossover design with three treatments (Treatments A, B, and C), six sequences, and three periods.

The relative bioavailability of 200 milligrams (mg) maribavir pediatric formulation administered orally as water suspension under fasting conditions (Treatment B) will be compared to 200 mg maribavir commercial tablet administered orally under fasting conditions (Treatment A). In addition, the effect of food on the pharmacokinetics (PK) of 200 mg maribavir pediatric formulation administered orally as water suspension under fasting conditions (Treatment B) and fed conditions (Treatment C) will be assessed. In each sequence, participants will receive three treatments (Treatments A, B, and C) per schedule.

• Sequence 1: Treatment A + Treatment B + Treatment C

• Sequence 2: Treatment A + Treatment C + Treatment B

• Sequence 3: Treatment B + Treatment A + Treatment C

• Sequence 4: Treatment B + Treatment C + Treatment A

• Sequence 5: Treatment C + Treatment A + Treatment B

• Sequence 6: Treatment C + Treatment B + Treatment A

Part 2 is a single fixed-sequence design with two treatments (Treatments D and E). The two treatments will be administered to evaluate the gastric acid-reducing effect of multiple doses of rabeprazole on the PK of a single dose of 200 mg maribavir pediatric formulation administered orally as water suspension.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: August 31, 2023
• Est. primary completion date: August 25, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• An understanding, ability, and willingness to fully comply with study procedures and restrictions and to voluntarily sign (personally or via a legally authorized representative) informed consent form to participate in the study.

• Age 18 to 55 years, inclusive at the time of consent, at the screening visit.

• Male, or non-pregnant, non-breastfeeding female who agrees to comply with any applicable contraceptive requirements of the protocol or female of non-childbearing potential.

• Body mass index (BMI) between 18.0 and 30.0 kilogram per meter square (kg/m^2), inclusive with a body weight greater than (>) 50 kilograms (kg) (110 pounds [lbs]), at the screening visit.

• Healthy as determined by the Investigator or designee on the basis of screening evaluations and medical history.

• Hemoglobin for males greater than or equal to (>=) 135.0 gram per liter (g/L) and females >=120.0 g/L, at the screening visit and on Day -1 of Treatment Period 1.

• Ability to swallow a dose of maribavir or rabeprazole.

Exclusion Criteria:

• History or presence of gastritis, gastrointestinal (GI) tract disorder, hepatic disorder or cholecystectomy, history of treated or untreated Helicobacter pylori, ulcer disease or other clinical condition which, in the opinion of the investigator or designee, may affect the absorption, distribution, metabolism, or elimination of the study drugs.

• History of any hematological, hepatic, respiratory, cardiovascular, renal, neurological or psychiatric disease, gall bladder removal, or current recurrent disease that could affect the action, absorption, or disposition of the study drugs, or clinical or laboratory assessments.

• Current or relevant history of physical or psychiatric illness, any medical disorder that may require treatment or make the participant unlikely to fully complete the study, or any condition that presents undue risk from the study drugs or procedures.

• Known or suspected intolerance or hypersensitivity to maribavir or rabeprazole (Part 2 only), closely related compounds, or any of the stated ingredients and excipients.

• Significant illness, as judged by the Investigator or designee, within 2 weeks of the first dose of the investigational drug (ID).

• Has diarrhea within 4 hours of the first dose of the ID.

• Donation of blood or blood products (example, plasma or platelets) within 60 days prior to receiving the first dose of the ID.

• Within 30 days prior to the first dose of the ID:

• Have used any investigational product (if elimination half-life is less than [<] 6 days, otherwise 5 half-lives).

• Have been enrolled in a clinical study (including vaccine studies) that, in the Investigator or designee's opinion, may impact this Takeda-sponsored study.

• Have had any substantial changes in eating habits, as assessed by the Investigator or designee.

• Systolic blood pressure >140 millimeters of mercury (mmHg) or <90 mmHg, and/or diastolic blood pressure >90 mmHg or <50 mmHg, at the screening visit.

• Corrected QT interval (QTc) >450 millisecond (msec) at the screening visit. If QTc exceeds 450 msec, the ECG should be repeated two more times and the average of the three QTc values should be used to determine the participant's eligibility.

• Known history of alcohol or other substance abuse within the last year.

• Male participants who consume more than 21 units of alcohol per week or three units per day. Female participants who consume more than 14 units of alcohol per week or two units per day (one alcohol unit = one beer or one wine [5 ounces [oz]/150 milliliter [mL]] or one liquor [1.5 oz/40 mL] or 0.75 oz alcohol).

• A positive screen for alcohol or drugs of abuse at the screening visit or on Day -1 of Treatment Period 1. Urine samples are to be tested for amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, opiates, and phencyclidine.

• A positive Human immunodeficiency virus (HIV), Hepatitis B surface antigen (HBsAg), or Hepatitis C virus (HCV) antibody screen at the screening visit.

• Use of tobacco in any form (example, smoking or chewing) or other nicotine-containing products in any form (example, gum, patch). Ex-users must self-report that they have stopped using tobacco for at least 3 months prior to receiving the first dose.

• Routine consumption of more than two units of caffeine per day or participants who experience caffeine withdrawal headaches (One caffeine unit is contained in the following items: one 6-oz [180 mL] cup of coffee, two 12-oz [360 mL] cans of cola, one 12-oz cup of tea, three 1-oz [85 grams [g]] chocolate bars). Decaffeinated coffee, tea, or cola are not considered to contain caffeine.

• Current use of any prescription medication with the exception of hormonal contraceptives and hormonal replacement therapy. Current use of any over-the-counter (OTC) medication (including OTC multi-vitamin, herbal, or homeopathic preparations) within 14 days of the first dose. Hormonal contraceptives and hormonal replacement therapy may be permitted if the female participant has been on the same stable dose for at least 3 months prior to first dose.

• Current use of antacids, proton pump inhibitors (PPIs), or histamine type 2 (H2) antagonists within 14 days of the first dose, except for on-study rabeprazole.

• Inability or unwillingness to consume 100 percent of the high-fat, high-calorie meal (including participants with lactose or gluten intolerance).

• Female participants with a positive pregnancy test at the screening visit or on Day -1 of Treatment Period 1 or who are lactating.

• Participants on a diet incompatible with the on-study diet, in the opinion of the Investigator or designee, within the 30 days prior to the first dosing and throughout the study.

• Recent history (within 1 month) of oral/nasal cavity infections, history of gastroesophageal reflux, asthma treatment with albuterol, or zinc supplementation.

• Participants with dry mouth syndrome or burning mouth syndrome or participants suffering from dysgeusia.

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• Maribavir Commercial Tablet Formulation
Maribavir commercial tablet.
• Maribavir Pediatric Powder-for-oral Suspension Formulation
Maribavir pediatric powder-for-oral suspension.
• Rabeprazole
Rabeprazole tablet.

Locations

Country	Name	City	State
United States	Celerion	Tempe	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Parts 1 and 2: Maximum Observed Plasma Concentration (Cmax) of maribavir	Cmax of maribavir in plasma will be assessed.	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours post-dose in each treatment period on Day 1 in Parts 1 and 2 and Day 5 in Part 2
Primary	Parts 1 and 2: Area Under the Plasma Concentration-time Curve from time 0 to the time of the last quantifiable concentration (AUClast) of maribavir	AUClast of maribavir in plasma will be assessed.	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours post-dose in each treatment period on Day 1 in Parts 1 and 2 and Day 5 in Part 2
Primary	Parts 1 and 2: Area Under the Plasma Concentration-time Curve from time 0 to infinity (AUC0-infinity) of maribavir	AUC0-infinity of maribavir in plasma will be assessed.	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours post-dose in each treatment period on Day 1 in Parts 1 and 2 and Day 5 in Part 2
Secondary	Parts 1 and 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	TEAEs will include TEAES by severity, TEAEs by causality, any clinically significant changes in vital signs, electrocardiogram (ECG) values and clinical laboratory parameters.	Parts 1 and 2: From start of study drug administration up to follow-up (Day 16)