Healthy Volunteers
Conditions
Brief 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.
Detailed 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.
Interventions
DRUGMaribavir (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.
DRUGMaribavir (200 mg)
Japanese descent group participants will receive 200 mg maribavir tablets orally once on Day 1 during treatment period 2 or 3.
DRUGMaribavir (800 mg)
Japanese descent group participants will receive 800 mg maribavir tablets orally once on Day 1 during treatment period 2 or 3.
Sponsors
Shire
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of Maribavir | 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 | Cmax of maribavir in plasma were reported. |
| Area Under the Plasma Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) of Maribavir | 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 | AUClast of maribavir in plasma were reported. |
| Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-infinity) of Maribavir | 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 | AUC(0-infinity) of maribavir in plasma were reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dose Proportionality of Cmax of Maribavir in Japanese Descent Participants | 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 | 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. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | From start of study drug administration to follow-up (up to Day 23) | 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. |
| Dose Proportionality of AUClast of Maribavir in Japanese Descent Participants | 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 | 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. |
| Dose Proportionality of AUC0-infinity of Maribavir in Japanese Descent Participants | 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 | 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. |
Countries
United States
Participant flow
Recruitment details
This study was conducted at single center in the United States from 07 Aug 2020 (first participant first visit) to 12 Nov 2020 (last participant last visit).
Pre-assignment details
A total of 24 participants (12 non-Hispanic Caucasian participants in Cohort A and 12 Japanese participants in Cohort B) were enrolled, randomized and received the study treatment in this study.
Participants by arm
| Arm | Count |
|---|---|
| Cohort A: Non-Hispanic, Caucasian Non-Hispanic, Caucasian participants received 400 mg maribavir tablets orally once on Day 1 during treatment period 1. | 12 |
| Cohort B: Japanese Descent Japanese descent participants received single dose of 400 mg maribavir tablets orally on Day 1 during treatment period 1 followed by single dose of 200 mg or 800 mg maribavir tablets orally on Day 1 during treatment period 2 followed by single dose of 800 mg or 200 mg maribavir tablets orally on Day 1 during treatment period 3 in cross-over fashion. A washout period of 72 hours was maintained between treatment period 1, 2, and 3. | 12 |
| Total | 24 |
Baseline characteristics
| Characteristic | Cohort B: Japanese Descent | Total | Cohort A: Non-Hispanic, Caucasian |
|---|---|---|---|
| Age, Continuous | 40.8 Years STANDARD_DEVIATION 8.92 | 40.0 Years STANDARD_DEVIATION 8.95 | 39.3 Years STANDARD_DEVIATION 9.33 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 24 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 12 Participants | 12 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 12 Participants | 12 Participants |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 2 Participants |
| Sex: Female, Male Male | 10 Participants | 20 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 4 / 12 | 2 / 12 | 1 / 12 | 0 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 12 |
Outcome results
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.
Time frame: 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
Population: The PK set consisted of participants who received at least 1 dose of maribavir and had evaluable post-dose maribavir PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort A: Maribavir 400 mg | Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-infinity) of Maribavir | 77.3 h*mcg/mL | Geometric Coefficient of Variation 34.7 |
| Cohort B: Maribavir 400 mg | Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-infinity) of Maribavir | 96.7 h*mcg/mL | Geometric Coefficient of Variation 37.1 |
| Cohort B: Maribavir 200 mg | Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-infinity) of Maribavir | 43.0 h*mcg/mL | Geometric Coefficient of Variation 42.4 |
| Cohort B: Maribavir 800 mg | Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-infinity) of Maribavir | 195 h*mcg/mL | Geometric Coefficient of Variation 43.9 |
Comparison: The comparison analysis was planned between Cohort A: Maribavir 400 mg and Cohort B: Maribavir 400 mg group participants only.90% CI: [97.99, 159.64]ANOVA
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.
Time frame: 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
Population: The PK set consisted of participants who received at least 1 dose of maribavir and had evaluable post-dose maribavir PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort A: Maribavir 400 mg | Area Under the Plasma Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) of Maribavir | 75.3 Hour*microgram per milliliter (h*mcg/mL) | Geometric Coefficient of Variation 33.6 |
| Cohort B: Maribavir 400 mg | Area Under the Plasma Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) of Maribavir | 92.3 Hour*microgram per milliliter (h*mcg/mL) | Geometric Coefficient of Variation 35.3 |
| Cohort B: Maribavir 200 mg | Area Under the Plasma Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) of Maribavir | 41.3 Hour*microgram per milliliter (h*mcg/mL) | Geometric Coefficient of Variation 40.8 |
| Cohort B: Maribavir 800 mg | Area Under the Plasma Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) of Maribavir | 183 Hour*microgram per milliliter (h*mcg/mL) | Geometric Coefficient of Variation 40.6 |
Comparison: The comparison analysis was planned between Cohort A: Maribavir 400 mg and Cohort B: Maribavir 400 mg group participants only.90% CI: [96.83, 154.95]ANOVA
Primary
Maximum Observed Plasma Concentration (Cmax) of Maribavir
Cmax of maribavir in plasma were reported.
Time frame: 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
Population: The pharmacokinetic (PK) set consisted of participants who received at least 1 dose of maribavir and had evaluable post-dose maribavir PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort A: Maribavir 400 mg | Maximum Observed Plasma Concentration (Cmax) of Maribavir | 15.8 Micrograms per milliliter (mcg/mL) | Geometric Coefficient of Variation 26.6 |
| Cohort B: Maribavir 400 mg | Maximum Observed Plasma Concentration (Cmax) of Maribavir | 17.4 Micrograms per milliliter (mcg/mL) | Geometric Coefficient of Variation 27.4 |
| Cohort B: Maribavir 200 mg | Maximum Observed Plasma Concentration (Cmax) of Maribavir | 9.03 Micrograms per milliliter (mcg/mL) | Geometric Coefficient of Variation 34 |
| Cohort B: Maribavir 800 mg | Maximum Observed Plasma Concentration (Cmax) of Maribavir | 26.3 Micrograms per milliliter (mcg/mL) | Geometric Coefficient of Variation 30.7 |
Comparison: The comparison analysis was planned between Cohort A: Maribavir 400 mg and Cohort B: Maribavir 400 mg group participants only.90% CI: [91.7, 132.94]ANOVA
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.
Time frame: 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
Population: The PK set consisted of participants who received at least 1 dose of maribavir and had evaluable post-dose maribavir PK data. Dose proportionality of AUC0-infinity of maribavir was planned to be evaluated in Japanese descent participants only.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A: Maribavir 400 mg | Dose Proportionality of AUC0-infinity of Maribavir in Japanese Descent Participants | 1.09 ln (AUC0-infnity[h*mcg/mL]) |
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.
Time frame: 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
Population: The PK set consisted of participants who received at least 1 dose of maribavir and had evaluable post-dose maribavir PK data. Dose proportionality of AUClast of maribavir was planned to be evaluated in Japanese descent participants only.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A: Maribavir 400 mg | Dose Proportionality of AUClast of Maribavir in Japanese Descent Participants | 1.07 ln (AUClast[h*mcg/mL]) |
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.
Time frame: 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
Population: The PK set consisted of participants who received at least 1 dose of maribavir and had evaluable post-dose maribavir PK data. Dose proportionality of Cmax of maribavir was planned to be evaluated in Japanese descent participants only.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A: Maribavir 400 mg | Dose Proportionality of Cmax of Maribavir in Japanese Descent Participants | 0.771 ln (Cmax [mcg/mL]) |
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.
Time frame: From start of study drug administration to follow-up (up to Day 23)
Population: The safety set consisted of participants who were administered at least 1 dose of maribavir and had at least 1 post-dose safety assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A: Maribavir 400 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with TEAEs | 4 Participants |
| Cohort A: Maribavir 400 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with serious TEAEs | 0 Participants |
| Cohort B: Maribavir 400 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with serious TEAEs | 0 Participants |
| Cohort B: Maribavir 400 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with TEAEs | 2 Participants |
| Cohort B: Maribavir 200 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with TEAEs | 1 Participants |
| Cohort B: Maribavir 200 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with serious TEAEs | 0 Participants |
| Cohort B: Maribavir 800 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with TEAEs | 0 Participants |
| Cohort B: Maribavir 800 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with serious TEAEs | 0 Participants |