A Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of a Single Oral Dose of Maribavir Administered in Healthy Japanese Participants Compared With Matched, Healthy, Non-Hispanic, Caucasian Participants and to Assess Dose-Proportionality of 3 Doses of Maribavir in Japanese Participants

Healthy Volunteers Clinical Trial

Official title:

A Phase 1, Open-label, Randomized, Cross-over Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of a Single Oral Dose of Maribavir Administered in Healthy Japanese Subjects Compared With Matched, Healthy, Non-Hispanic, Caucasian Subjects and to Assess Dose-Proportionality of 3 Doses of Maribavir in the Japanese Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04497883
• Other study ID #: TAK-620-1020
• Status: Completed
• Phase: Phase 1
• Start date: August 7, 2020
• Est. completion date: November 12, 2020

Study information

• Verified date: February 2022
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to compare the pharmacokinetics (PK), safety, and tolerability of maribavir administered as a single oral dose in healthy, adult participants of Japanese descent and matched, healthy, adult, non-Hispanic, Caucasian participants. In addition, this study will assess the dose-proportionality of PK of maribavir in healthy, adult participants of Japanese descent.

Description:

The study will be conducted in two cohorts, Cohort A and Cohort B. Cohort A consists of 12 participants of Japanese Descent. Cohort B consists of 12 non-Hispanic, Caucasian participants.

For Japanese participants there will be three treatment periods. In Treatment Period 1, they will receive maribavir as a single 400 mg oral dose. In Treatment Periods 2 and 3, all Japanese participants will receive maribavir as a single oral dose of either 200 mg or 800 mg, depending upon randomization assignment. For the non-Hispanic, Caucasian group there will be only one treatment period and they will receive maribavir as a single 400 mg oral dose.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: November 12, 2020
• Est. primary completion date: November 12, 2020
• 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.

• Ability to voluntarily provide written informed consent/assent as applicable to participate in the study.

• Healthy 18 to 55 years old participants of Japanese descent and non-Hispanic Caucasian origin.

• Healthy participants of Japanese descent must have been born in Japan and must not have lived outside of Japan for greater than (>) 10 years; both parents and all 4 grandparents must be of Japanese origin. Healthy, non-Hispanic, Caucasian participants must have both parents and all 4 grandparents of non-Hispanic, Caucasian origin.

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

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

• Body mass index (BMI) between 18.5 and 28.0 kilogram per square meter (kg/m^2) inclusive with a body weight > 45 kilograms (kg) (99 pounds [lbs]).

• Ability to swallow a dose of investigational product (IP).

Exclusion Criteria:

• History of any hematological, hepatic, respiratory, cardiovascular, renal, neurological, or psychiatric disease, gall bladder removal, or current recurrent disease.

• 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 IP or procedures.

• Known or suspected intolerance or hypersensitivity to maribavir, closely-related compounds, or any of the stated ingredients.

• Significant illness, as judged by the investigator, within 2 weeks of the first dose of IP.

• Donation of blood or blood products (e.g. plasma or platelets) within 60 days prior to receiving the first dose of IP.

• Have taken another IP within 30 days or five half-lives of that IP, whichever is greater, prior to the first dose of maribavir.

• Have been enrolled in a clinical study (including vaccine studies) within 30 days prior to the first dose of IP that, in the investigator's opinion, may impact this study.

• Have had any substantial changes in eating habits within 30 days prior to the first dose of IP, as assessed by the investigator.

• Confirmed systolic blood pressure > 139 millimeter of mercury (mmHg) or less than (<) 89 mmHg, and diastolic blood pressure > 89 mmHg or < 49 mmHg.

• Twelve-lead ECG demonstrating QTc > 450 milliseconds (msec).

• Known history of alcohol or other substance abuse, including synthetic cannabinoids within the last year.

• Male participants who consume more than 21 units of alcohol per week or 3 units per day. Female participants who consume more than 14 units of alcohol per week or 2 units per day.

• A positive urine test for drugs of abuse, alcohol, or cotinine at screening or on Day -1.

• A positive human immunodeficiency virus (HIV), hepatitis B surface antibody (HBsAg), or hepatitis C virus (HCV) antibody screen.

• Use of tobacco in any form (e.g. smoking or chewing) or other nicotine-containing products in any form (e.g. gum, patch).

• Routine consumption of more than 2 units of caffeine per day or participants who experience caffeine withdrawal headaches.

• Current use of any prescription medication within 30 days of the first dose of IP. Current use of any over the counter medication within 14 days of the first dose of IP.

• Ingestion of known cytochrome P450 (CYP) 3A modulators within 7 days of Day 1, period 1

• History of active or chronic oral/nasal cavity infections, gastroesophageal reflux, asthma treatment with albuterol, zinc supplementation.

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

• Participants who have acute gastrointestinal (GI) symptoms at screening or admission (e.g. nausea, vomiting, diarrhea, and heartburn).

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• Maribavir (400 mg)
Non-Hispanic, Caucasian group and Japanese descent group participants will receive 400 mg maribavir tablets orally once on Day 1 during treatment period 1.
• Maribavir (200 mg)
Japanese descent group participants will receive 200 mg maribavir tablets orally once on Day 1 during treatment period 2 or 3.
• Maribavir (800 mg)
Japanese descent group participants will receive 800 mg maribavir tablets orally once on Day 1 during treatment period 2 or 3.

Locations

Country	Name	City	State
United States	PPD Development, LP	Las Vegas	Nevada

Sponsors (1)

Lead Sponsor	Collaborator
Shire

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Observed Plasma Concentration (Cmax) of Maribavir	Cmax of maribavir in plasma were reported.	Day 1 of each treatment period: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 20, and 24 hours post-dose
Primary	Area Under the Plasma Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) of Maribavir	AUClast of maribavir in plasma were reported.	Day 1 of each treatment period: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 20, and 24 hours post-dose
Primary	Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-infinity) of Maribavir	AUC(0-infinity) of maribavir in plasma were reported.	Day 1 of each treatment period: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 20, and 24 hours post-dose
Secondary	Dose Proportionality of Cmax of Maribavir in Japanese Descent Participants	Dose proportionality was assessed using the power model including log-transformed Cmax dependent variable and the log-transformed dose as a fixed effect. Natural log (ln) and 90% confidence interval for the slope are presented.	Day 1 of each treatment period: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 20, and 24 hours post-dose
Secondary	Dose Proportionality of AUClast of Maribavir in Japanese Descent Participants	Dose proportionality was assessed using the power model including log-transformed AUClast dependent variable and the log-transformed dose as a fixed effect. ln and 90% confidence interval for the slope are presented.	Day 1 of each treatment period: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 20, and 24 hours post-dose
Secondary	Dose Proportionality of AUC0-infinity of Maribavir in Japanese Descent Participants	Dose proportionality was assessed using the power model including log-transformed AUC0-inifinity dependent variable and the log-transformed dose as a fixed effect. ln and 90% confidence interval for the slope are presented.	Day 1 of each treatment period: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 20, and 24 hours post-dose
Secondary	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs	An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily had a causal relationship with this investigational product (IP) or medicinal product. An SAE was any untoward medical occurrence that at any dose met one, more of the following criteria: results in death, life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent, significant disability/incapacity, a congenital abnormality/birth defect, an important medical event. A TEAE was any event emerging or manifesting at or after the initiation of treatment with an IP or medicinal product or any existing event that worsens in either intensity or frequency following exposure to the IP or medicinal product. Number of Participants with TEAEs and serious TEAEs were reported in both non-Hispanic, Caucasian and Japanese descent participants.	From start of study drug administration to follow-up (up to Day 23)

External Links

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