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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort A: Non-Hispanic, Caucasian | Experimental | Non-Hispanic, Caucasian group participants will receive 400 milligram (mg) maribavir tablets orally once on Day 1 during treatment period 1. |
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| Cohort B: Japanese Descent | Experimental | Japanese descent group participants will receive 400 mg maribavir tablets orally once on Day 1 during treatment period 1 followed by 200 mg or 800 mg maribavir tablets orally once on Day 1 during treatment period 2 followed by 800 mg or 200 mg maribavir tablets orally once on Day 1 during treatment period 3 in cross-over fashion. A washout period of 72 hours will be maintained between treatment period 1, 2, and 3. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Maribavir (400 mg) | Drug | Non-Hispanic, Caucasian group and Japanese descent group participants will receive 400 mg maribavir tablets orally once on Day 1 during treatment period 1. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| 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 |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Study Director | Shire | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| PPD Development, LP | Las Vegas | Nevada | 89113 | United States |
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| Label | URL |
|---|---|
| To obtain more information on the study, click here/on this link | View source |
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De-identified individual participant data from this particular study will not be shared as the data are subject to contractual (or consent) provisions that prohibit transfer to third parties.
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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.
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).
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort A: Non-Hispanic, Caucasian | Non-Hispanic, Caucasian participants received single dose of 400 milligram (mg) maribavir tablets orally on Day 1 during treatment period 1. |
| FG001 | Cohort B: Japanese Descent: Maribavir 400mg |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Treatment Period 1 (2 Days) |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jul 8, 2020 | Aug 27, 2021 |
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| Maribavir (200 mg) | Drug | Japanese descent group participants will receive 200 mg maribavir tablets orally once on Day 1 during treatment period 2 or 3. |
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| Maribavir (800 mg) | Drug | Japanese descent group participants will receive 800 mg maribavir tablets orally once on Day 1 during treatment period 2 or 3. |
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| 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 |
| 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 |
| 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) |
Japanese descent participants received single oral dose of 400 mg maribavir tablets on Day 1 during treatment period 1.
| FG002 | Cohort B: Japanese Descent: First Maribavir 200 mg Then Maribavir 800 mg | Japanese descent participants who received 400 mg maribavir tablets during treatment period 1 received single dose of 200 mg maribavir tablet orally on Day 1 during treatment period 2 followed by single dose of 800 mg maribavir tablets orally on Day 1 during treatment period 3. A washout period of 72 hours was maintained between treatment period 1, 2, and 3. |
| FG003 | Cohort B: Japanese Descent: First Maribavir 800 mg Then Maribavir 200 mg | Japanese descent participants who received 400 mg maribavir tablets during treatment period 1 received single dose of 800 mg maribavir tablets orally on Day 1 during treatment period 2 followed by single dose of 200 mg maribavir tablet orally on Day 1 during treatment period 3. A washout period of 72 hours was maintained between treatment period 1, 2, and 3. |
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| NOT COMPLETED |
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| Washout Period 1 (72 Hours) |
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| Treatment Period 2 (2 Days) |
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| Washout Period 2 (72 Hours) |
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| Treatment Period 3 (2 Days) |
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The safety set consisted of participants who were administered at least 1 dose of maribavir and had at least 1 post-dose safety assessment.
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort A: Non-Hispanic, Caucasian | Non-Hispanic, Caucasian participants received 400 mg maribavir tablets orally once on Day 1 during treatment period 1. |
| BG001 | 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. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
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| Age, Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Maximum Observed Plasma Concentration (Cmax) of Maribavir | Cmax of maribavir in plasma were reported. | The pharmacokinetic (PK) set consisted of participants who received at least 1 dose of maribavir and had evaluable post-dose maribavir PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | Micrograms per milliliter (mcg/mL) | 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 |
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| 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. | The PK set consisted of participants who received at least 1 dose of maribavir and had evaluable post-dose maribavir PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hour*microgram per milliliter (h*mcg/mL) | 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 |
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| 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. | The PK set consisted of participants who received at least 1 dose of maribavir and had evaluable post-dose maribavir PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*mcg/mL | 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 |
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| 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. | 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. | Posted | Number | 90% Confidence Interval | ln (Cmax [mcg/mL]) | 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 |
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| 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. | 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. | Posted | Number | 90% Confidence Interval | ln (AUClast[h*mcg/mL]) | 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 |
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| 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. | 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. | Posted | Number | 90% Confidence Interval | ln (AUC0-infnity[h*mcg/mL]) | 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 |
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| 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. | The safety set consisted of participants who were administered at least 1 dose of maribavir and had at least 1 post-dose safety assessment. | Posted | Count of Participants | Participants | From start of study drug administration to follow-up (up to Day 23) |
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From start of study drug administration to follow-up (up to Day 23)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
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| EG000 | Cohort A: Maribavir 400 mg | Non-Hispanic, Caucasian participants received single oral dose of 400 mg maribavir tablets on Day 1 during treatment period 1. | 0 | 12 | 0 | 12 | 4 | 12 |
| EG001 | Cohort B: Maribavir 400 mg | Japanese descent participants received single oral dose of 400 mg maribavir tablets on Day 1 during treatment period 1. | 0 | 12 | 0 | 12 | 2 | 12 |
| EG002 | Cohort B: Maribavir 200 mg | Japanese descent participants received single oral dose of 200 mg maribavir tablets on Day 1 during treatment period 2 or 3. | 0 | 12 | 0 | 12 | 1 | 12 |
| EG003 | Cohort B: Maribavir 800 mg | Japanese descent participants received single oral dose of 800 mg maribavir tablets on Day 1 during treatment period 2 or 3. | 0 | 12 | 0 | 12 | 0 | 12 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
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| Dysgeusia | Nervous system disorders | MedDRA 23.0 | Non-systematic Assessment |
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| Somnolence | Nervous system disorders | MedDRA 23.0 | Non-systematic Assessment |
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If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Shire | +1 866 842 5335 | ClinicalTransparency@takeda.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 6, 2020 | Aug 27, 2021 | SAP_001.pdf |
| ID | Term |
|---|---|
| C400401 | maribavir |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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Japanese descent participants received single oral dose of 800 mg maribavir tablets on Day 1 during treatment period 2 or 3. |
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Japanese descent participants received single oral dose of 800 mg maribavir tablets on Day 1 during treatment period 2 or 3. |
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Japanese descent participants received single oral dose of 400 mg maribavir tablets on Day 1 during treatment period 1.
| OG002 | Cohort B: Maribavir 200 mg | Japanese descent participants received single oral dose of 200 mg maribavir tablets on Day 1 during treatment period 2 or 3. |
| OG003 | Cohort B: Maribavir 800 mg | Japanese descent participants received single oral dose of 800 mg maribavir tablets on Day 1 during treatment period 2 or 3. |
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