Trial Outcomes & Findings for Study of SHP620 (Maribavir) in Healthy Adults (NCT NCT02775240)

NCT ID: NCT02775240

Last Updated: 2021-06-03

Results Overview

Cmax is the maximum observed plasma concentration of digoxin.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 18 participants
• Primary outcome timeframe: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B
• Results posted on: 2021-06-03

Participant Flow

The study was conducted in a single center in the United States between 16 August 2016 (first participant first visit) and 31 August 2016 (last participant last visit).

A total of 18 participants were screened and were enrolled in the study and received the treatment.

Participant milestones

Measure	Treatment A and B On Day 1, participants received a single 0.5 mg (2 × 0.25 mg) oral dose of digoxin and a single 30 mg (2 x 15 mg) oral dose of dextromethorphan (Treatment A) followed by a wash out period of minimum 7 days until start of treatment B, during which participants received maribavir 400 mg (2 x 200 mg) orally twice daily from Day 8 to Day 15. On Day 13, participants received a single 0.5 mg (2 × 0.25 mg) oral dose of digoxin and a single 30 mg (2 × 15 mg) oral dose of dextromethorphan co-administered with the morning dose of maribavir. The test product, maribavir and the investigational products, digoxin and dextromethorphan, were provided in the form of tablet.
Overall Study STARTED	18
Overall Study Started Treatment A	18
Overall Study Started Treatment B	17
Overall Study COMPLETED	17
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study of SHP620 (Maribavir) in Healthy Adults

Baseline characteristics by cohort

Measure	Treatment A and B n=18 Participants On Day 1, participants received a single 0.5 mg (2 × 0.25 mg) oral dose of digoxin and a single 30 mg (2 x 15 mg) oral dose of dextromethorphan (Treatment A) followed by a wash out period of minimum 7 days until start of treatment B, during which participants received maribavir 400 mg (2 x 200 mg) orally twice daily from Day 8 to Day 15. On Day 13, participants received a single 0.5 mg (2 × 0.25 mg) oral dose of digoxin and a single 30 mg (2 × 15 mg) oral dose of dextromethorphan co-administered with the morning dose of maribavir. The test product, maribavir and the investigational products, digoxin and dextromethorphan, were provided in the form of tablet.
Age, Continuous	38.1 Year STANDARD_DEVIATION 8.72 • n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants

PRIMARY outcome

Timeframe: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B

Population: Pharmacokinetic (PK) set consisted of all participants who received at least 1 dose of investigational product and had evaluable PK data (defined as complete concentration-time profile to obtain meaningful estimates of PK parameters) available for 1 dose regimen.

Cmax is the maximum observed plasma concentration of digoxin.

Outcome measures

Measure	Treatment A n=18 Participants Participants received a single 0.5 mg (2 x 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 x 15 mg) oral dose of dextromethorphan tablet on Day 1.	Treatment B n=17 Participants Participants received maribavir 400 mg (2 x 200 mg) tablet orally twice daily from Day 8 to Day 15. On Day 13, participants received a single 0.5 mg (2 × 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 × 15 mg) oral dose of dextromethorphan tablet co-administered with the morning dose of maribavir.
Maximum Observed Plasma Concentration (Cmax) of Digoxin	1.94 Nanogram per milliliter (ng/mL) Interval 1.6 to 2.36	2.35 Nanogram per milliliter (ng/mL) Interval 1.98 to 2.8

PRIMARY outcome

Timeframe: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B

Population: PK set consisted of all participants who received at least 1 dose of investigational product and had evaluable PK data (defined as complete concentration-time profile to obtain meaningful estimates of PK parameters) available for 1 dose regimen.

Cmax is the maximum observed plasma concentration of dextromethorphan.

Outcome measures

Measure	Treatment A n=18 Participants Participants received a single 0.5 mg (2 x 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 x 15 mg) oral dose of dextromethorphan tablet on Day 1.	Treatment B n=17 Participants Participants received maribavir 400 mg (2 x 200 mg) tablet orally twice daily from Day 8 to Day 15. On Day 13, participants received a single 0.5 mg (2 × 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 × 15 mg) oral dose of dextromethorphan tablet co-administered with the morning dose of maribavir.
Maximum Observed Plasma Concentration (Cmax) of Dextromethorphan	1.14 Nanogram per milliliter (ng/mL) Interval 0.63 to 2.06	1.14 Nanogram per milliliter (ng/mL) Interval 0.65 to 1.99

PRIMARY outcome

Timeframe: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B

Population: PK set consisted of all participants who received at least 1 dose of investigational product and had evaluable PK data (defined as complete concentration-time profile to obtain meaningful estimates of PK parameters) available for 1 dose regimen.

Cmax is the maximum observed plasma concentration of dextrorphan, the metabolite of dextromethorphan.

Outcome measures

Measure	Treatment A n=18 Participants Participants received a single 0.5 mg (2 x 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 x 15 mg) oral dose of dextromethorphan tablet on Day 1.	Treatment B n=17 Participants Participants received maribavir 400 mg (2 x 200 mg) tablet orally twice daily from Day 8 to Day 15. On Day 13, participants received a single 0.5 mg (2 × 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 × 15 mg) oral dose of dextromethorphan tablet co-administered with the morning dose of maribavir.
Maximum Observed Plasma Concentration (Cmax) of Dextrorphan	433 Nanogram per milliliter (ng/mL) Interval 347.0 to 539.0	401 Nanogram per milliliter (ng/mL) Interval 324.0 to 496.0

PRIMARY outcome

Timeframe: Pre-dose, 0.25,0.5,1,1.5,2,3,4,5,6,8,12 hours post-dose on Day 13

Population: PK set consisted of all participants who received at least 1 dose of investigational product and had evaluable PK data (defined as complete concentration-time profile to obtain meaningful estimates of PK parameters) available for 1 dose regimen.

Cmax is the maximum observed plasma concentration of maribavir.

Outcome measures

Measure	Treatment A n=17 Participants Participants received a single 0.5 mg (2 x 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 x 15 mg) oral dose of dextromethorphan tablet on Day 1.	Treatment B Participants received maribavir 400 mg (2 x 200 mg) tablet orally twice daily from Day 8 to Day 15. On Day 13, participants received a single 0.5 mg (2 × 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 × 15 mg) oral dose of dextromethorphan tablet co-administered with the morning dose of maribavir.
Maximum Observed Plasma Concentration (Cmax) of Maribavir	17.6 Microgram per milliliter (mcg/mL) Interval 15.5 to 19.9	—

PRIMARY outcome

Timeframe: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B

Population: PK set consisted of all participants who received at least 1 dose of investigational product and had evaluable PK data (defined as complete concentration-time profile to obtain meaningful estimates of PK parameters) available for 1 dose regimen.

Tmax is the time to reach the maximum observed drug concentration in plasma during a dosing interval.

Outcome measures

Measure	Treatment A n=18 Participants Participants received a single 0.5 mg (2 x 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 x 15 mg) oral dose of dextromethorphan tablet on Day 1.	Treatment B n=17 Participants Participants received maribavir 400 mg (2 x 200 mg) tablet orally twice daily from Day 8 to Day 15. On Day 13, participants received a single 0.5 mg (2 × 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 × 15 mg) oral dose of dextromethorphan tablet co-administered with the morning dose of maribavir.
Time to Reach Maximum Plasma Concentration (Tmax) of Digoxin	1.00 Hour (h) Interval 0.5 to 1.5	1.00 Hour (h) Interval 0.5 to 2.0

PRIMARY outcome

Timeframe: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B

Population: PK set consisted of all participants who received at least 1 dose of investigational product and had evaluable PK data (defined as complete concentration-time profile to obtain meaningful estimates of PK parameters) available for 1 dose regimen.

Tmax is the time to reach the maximum observed drug concentration in plasma during a dosing interval.

Outcome measures

Measure	Treatment A n=18 Participants Participants received a single 0.5 mg (2 x 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 x 15 mg) oral dose of dextromethorphan tablet on Day 1.	Treatment B n=17 Participants Participants received maribavir 400 mg (2 x 200 mg) tablet orally twice daily from Day 8 to Day 15. On Day 13, participants received a single 0.5 mg (2 × 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 × 15 mg) oral dose of dextromethorphan tablet co-administered with the morning dose of maribavir.
Time to Reach Maximum Plasma Concentration (Tmax) of Dextromethorphan	3.00 Hour (h) Interval 1.5 to 5.0	3.00 Hour (h) Interval 2.0 to 5.0

PRIMARY outcome

Timeframe: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B

Population: PK set consisted of all participants who received at least 1 dose of investigational product and had evaluable PK data (defined as complete concentration-time profile to obtain meaningful estimates of PK parameters) available for 1 dose regimen.

Tmax is the time to reach the maximum observed drug concentration in plasma during a dosing interval.

Outcome measures

Measure	Treatment A n=18 Participants Participants received a single 0.5 mg (2 x 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 x 15 mg) oral dose of dextromethorphan tablet on Day 1.	Treatment B n=17 Participants Participants received maribavir 400 mg (2 x 200 mg) tablet orally twice daily from Day 8 to Day 15. On Day 13, participants received a single 0.5 mg (2 × 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 × 15 mg) oral dose of dextromethorphan tablet co-administered with the morning dose of maribavir.
Time to Reach Maximum Plasma Concentration (Tmax) of Dextrorphan	2.00 Hour (h) Interval 1.5 to 3.0	2.00 Hour (h) Interval 1.0 to 4.0

PRIMARY outcome

Timeframe: Pre-dose, 0.25,0.5,1,1.5,2,3,4,5,6,8,12 hours post-dose on Day 13

Population: PK set consisted of all participants who received at least 1 dose of investigational product and had evaluable PK data (defined as complete concentration-time profile to obtain meaningful estimates of PK parameters) available for 1 dose regimen.

Tmax is the time to reach the maximum observed drug concentration in plasma during a dosing interval.

Outcome measures

Measure	Treatment A n=17 Participants Participants received a single 0.5 mg (2 x 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 x 15 mg) oral dose of dextromethorphan tablet on Day 1.	Treatment B Participants received maribavir 400 mg (2 x 200 mg) tablet orally twice daily from Day 8 to Day 15. On Day 13, participants received a single 0.5 mg (2 × 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 × 15 mg) oral dose of dextromethorphan tablet co-administered with the morning dose of maribavir.
Time to Reach Maximum Plasma Concentration (Tmax) of Maribavir	2.00 Hour (h) Interval 0.5 to 3.0	—

PRIMARY outcome

Timeframe: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B

Population: PK set consisted of all participants who received at least 1 dose of investigational product and had evaluable PK data (defined as complete concentration-time profile to obtain meaningful estimates of PK parameters) available for 1 dose regimen.

AUC0-infinity is the area under the plasma concentration versus time curve extrapolated to infinity, calculated using the observed value of the last non-zero concentration.

Outcome measures

Measure	Treatment A n=18 Participants Participants received a single 0.5 mg (2 x 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 x 15 mg) oral dose of dextromethorphan tablet on Day 1.	Treatment B n=17 Participants Participants received maribavir 400 mg (2 x 200 mg) tablet orally twice daily from Day 8 to Day 15. On Day 13, participants received a single 0.5 mg (2 × 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 × 15 mg) oral dose of dextromethorphan tablet co-administered with the morning dose of maribavir.
Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Digoxin	31.6 Nanogram*hour per milliliter (ng*h/mL) Interval 26.9 to 37.2	37.3 Nanogram*hour per milliliter (ng*h/mL) Interval 32.9 to 42.2

PRIMARY outcome

Timeframe: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B

Population: PK set consisted of all participants who received at least 1 dose of investigational product and had evaluable PK data (defined as complete concentration-time profile to obtain meaningful estimates of PK parameters) available for 1 dose regimen.

AUC0-infinity is the area under the plasma concentration versus time curve extrapolated to infinity, calculated using the observed value of the last non-zero concentration.

Outcome measures

Measure	Treatment A n=5 Participants Participants received a single 0.5 mg (2 x 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 x 15 mg) oral dose of dextromethorphan tablet on Day 1.	Treatment B n=5 Participants Participants received maribavir 400 mg (2 x 200 mg) tablet orally twice daily from Day 8 to Day 15. On Day 13, participants received a single 0.5 mg (2 × 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 × 15 mg) oral dose of dextromethorphan tablet co-administered with the morning dose of maribavir.
Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Dextromethorphan Participant 1	290.74 Nanogram*hour per milliliter (ng*h/mL)	179.19 Nanogram*hour per milliliter (ng*h/mL)
Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Dextromethorphan Participant 2	28.10 Nanogram*hour per milliliter (ng*h/mL)	NA Nanogram*hour per milliliter (ng*h/mL) Terminal phase was not available for this participant.
Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Dextromethorphan Participant 3	NA Nanogram*hour per milliliter (ng*h/mL) Terminal phase was not available for this profile.	25.14 Nanogram*hour per milliliter (ng*h/mL)
Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Dextromethorphan Participant 4	168.69 Nanogram*hour per milliliter (ng*h/mL)	95.95 Nanogram*hour per milliliter (ng*h/mL)
Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Dextromethorphan Participant 5	48.33 Nanogram*hour per milliliter (ng*h/mL)	41.65 Nanogram*hour per milliliter (ng*h/mL)
Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Dextromethorphan Participant 6	26.79 Nanogram*hour per milliliter (ng*h/mL)	18.08 Nanogram*hour per milliliter (ng*h/mL)

PRIMARY outcome

Timeframe: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B

Population: PK set consisted of all participants who received at least 1 dose of investigational product and had evaluable PK data (defined as complete concentration-time profile to obtain meaningful estimates of PK parameters) available for 1 dose regimen.

AUC0-infinity is the area under the plasma concentration versus time curve extrapolated to infinity, calculated using the observed value of the last non-zero concentration.

Outcome measures

Measure	Treatment A n=18 Participants Participants received a single 0.5 mg (2 x 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 x 15 mg) oral dose of dextromethorphan tablet on Day 1.	Treatment B n=17 Participants Participants received maribavir 400 mg (2 x 200 mg) tablet orally twice daily from Day 8 to Day 15. On Day 13, participants received a single 0.5 mg (2 × 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 × 15 mg) oral dose of dextromethorphan tablet co-administered with the morning dose of maribavir.
Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Dextrorphan	2270 Nanogram*hour per milliliter (ng*h/mL) Interval 2050.0 to 2520.0	2150 Nanogram*hour per milliliter (ng*h/mL) Interval 1940.0 to 2390.0

PRIMARY outcome

Timeframe: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B

Population: PK set consisted of all participants who received at least 1 dose of investigational product and had evaluable PK data (defined as complete concentration-time profile to obtain meaningful estimates of PK parameters) available for 1 dose regimen.

AUClast is the area under the plasma concentration versus time curve from the time of dosing to the last measurable concentration.

Outcome measures

Measure	Treatment A n=18 Participants Participants received a single 0.5 mg (2 x 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 x 15 mg) oral dose of dextromethorphan tablet on Day 1.	Treatment B n=17 Participants Participants received maribavir 400 mg (2 x 200 mg) tablet orally twice daily from Day 8 to Day 15. On Day 13, participants received a single 0.5 mg (2 × 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 × 15 mg) oral dose of dextromethorphan tablet co-administered with the morning dose of maribavir.
Area Under the Plasma Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) of Digoxin	23.0 Nanogram*hour per milliliter (ng*h/mL) Interval 19.9 to 26.6	26.7 Nanogram*hour per milliliter (ng*h/mL) Interval 24.3 to 29.4

PRIMARY outcome

Timeframe: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B

Population: PK set consisted of all participants who received at least 1 dose of investigational product and had evaluable PK data (defined as complete concentration-time profile to obtain meaningful estimates of PK parameters) available for 1 dose regimen.

AUClast is the area under the plasma concentration versus time curve from the time of dosing to the last measurable concentration.

Outcome measures

Measure	Treatment A n=18 Participants Participants received a single 0.5 mg (2 x 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 x 15 mg) oral dose of dextromethorphan tablet on Day 1.	Treatment B n=17 Participants Participants received maribavir 400 mg (2 x 200 mg) tablet orally twice daily from Day 8 to Day 15. On Day 13, participants received a single 0.5 mg (2 × 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 × 15 mg) oral dose of dextromethorphan tablet co-administered with the morning dose of maribavir.
Area Under the Plasma Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) of Dextromethorphan	7.06 Nanogram*hour per milliliter (ng*h/mL) Interval 3.09 to 16.1	6.77 Nanogram*hour per milliliter (ng*h/mL) Interval 3.02 to 15.2

PRIMARY outcome

Timeframe: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B

Population: PK set consisted of all participants who received at least 1 dose of investigational product and had evaluable PK data (defined as complete concentration-time profile to obtain meaningful estimates of PK parameters) available for 1 dose regimen.

AUClast is the area under the plasma concentration versus time curve from the time of dosing to the last measurable concentration.

Outcome measures

Measure	Treatment A n=18 Participants Participants received a single 0.5 mg (2 x 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 x 15 mg) oral dose of dextromethorphan tablet on Day 1.	Treatment B n=17 Participants Participants received maribavir 400 mg (2 x 200 mg) tablet orally twice daily from Day 8 to Day 15. On Day 13, participants received a single 0.5 mg (2 × 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 × 15 mg) oral dose of dextromethorphan tablet co-administered with the morning dose of maribavir.
Area Under the Plasma Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) of Dextrorphan	2200 Nanogram*hour per milliliter (ng*h/mL) Interval 1980.0 to 2450.0	2110 Nanogram*hour per milliliter (ng*h/mL) Interval 1890.0 to 2360.0

PRIMARY outcome

Timeframe: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B

Population: PK set consisted of all participants who received at least 1 dose of investigational product and had evaluable PK data (defined as complete concentration-time profile to obtain meaningful estimates of PK parameters) available for 1 dose regimen.

AUClast parent/metabolite ratio is the ratio of AUClast for dextromethorphan over AUClast for dextrorphan.

Outcome measures

Measure	Treatment A n=18 Participants Participants received a single 0.5 mg (2 x 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 x 15 mg) oral dose of dextromethorphan tablet on Day 1.	Treatment B n=17 Participants Participants received maribavir 400 mg (2 x 200 mg) tablet orally twice daily from Day 8 to Day 15. On Day 13, participants received a single 0.5 mg (2 × 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 × 15 mg) oral dose of dextromethorphan tablet co-administered with the morning dose of maribavir.
Parent/Metabolite Ratio of Area Under the Plasma Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) for Dextromethorphan Over AUClast for Dextrorphan (AUClast Parent/Metabolite Ratio)	0.003 Ratio of AUClast Interval 0.001 to 0.008	0.003 Ratio of AUClast Interval 0.001 to 0.008

PRIMARY outcome

Timeframe: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B

Population: PK set consisted of all participants who received at least 1 dose of investigational product and had evaluable PK data (defined as complete concentration-time profile to obtain meaningful estimates of PK parameters) available for 1 dose regimen.

AUC0-infinity parent/metabolite ratio is the ratio of AUC0-infinity for dextromethorphan over AUC0-infinity for dextrorphan.

Outcome measures

Measure	Treatment A n=5 Participants Participants received a single 0.5 mg (2 x 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 x 15 mg) oral dose of dextromethorphan tablet on Day 1.	Treatment B n=5 Participants Participants received maribavir 400 mg (2 x 200 mg) tablet orally twice daily from Day 8 to Day 15. On Day 13, participants received a single 0.5 mg (2 × 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 × 15 mg) oral dose of dextromethorphan tablet co-administered with the morning dose of maribavir.
Parent/Metabolite Ratio of Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) for Dextromethorphan Over AUC0-infinity for Dextrorphan (AUC0-infinity Parent/Metabolite Ratio) Participant 1	0.177 Ratio of AUC0-infinity	0.127 Ratio of AUC0-infinity
Parent/Metabolite Ratio of Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) for Dextromethorphan Over AUC0-infinity for Dextrorphan (AUC0-infinity Parent/Metabolite Ratio) Participant 2	0.009 Ratio of AUC0-infinity	NA Ratio of AUC0-infinity Terminal phase was not available for this participant.
Parent/Metabolite Ratio of Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) for Dextromethorphan Over AUC0-infinity for Dextrorphan (AUC0-infinity Parent/Metabolite Ratio) Participant 3	NA Ratio of AUC0-infinity Terminal phase was not available for this participant.	0.014 Ratio of AUC0-infinity
Parent/Metabolite Ratio of Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) for Dextromethorphan Over AUC0-infinity for Dextrorphan (AUC0-infinity Parent/Metabolite Ratio) Participant 4	0.096 Ratio of AUC0-infinity	0.056 Ratio of AUC0-infinity
Parent/Metabolite Ratio of Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) for Dextromethorphan Over AUC0-infinity for Dextrorphan (AUC0-infinity Parent/Metabolite Ratio) Participant 5	0.028 Ratio of AUC0-infinity	0.025 Ratio of AUC0-infinity
Parent/Metabolite Ratio of Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) for Dextromethorphan Over AUC0-infinity for Dextrorphan (AUC0-infinity Parent/Metabolite Ratio) Participant 6	0.013 Ratio of AUC0-infinity	0.008 Ratio of AUC0-infinity

PRIMARY outcome

Timeframe: Pre-dose, 0.25,0.5,1,1.5,2,3,4,5,6,8,12 hours post-dose on Day 13

Population: PK set consisted of all participants who received at least 1 dose of investigational product and had evaluable PK data (defined as complete concentration-time profile to obtain meaningful estimates of PK parameters) available for 1 dose regimen.

AUCtau is the area under the plasma concentration versus time curve from the time zero to the end of the dosing interval at steady-state.

Outcome measures

Measure	Treatment A n=17 Participants Participants received a single 0.5 mg (2 x 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 x 15 mg) oral dose of dextromethorphan tablet on Day 1.	Treatment B Participants received maribavir 400 mg (2 x 200 mg) tablet orally twice daily from Day 8 to Day 15. On Day 13, participants received a single 0.5 mg (2 × 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 × 15 mg) oral dose of dextromethorphan tablet co-administered with the morning dose of maribavir.
Area Under the Plasma Concentration Versus Time Curve From Time Zero to the End of the Dosing Interval at Steady-State (AUCtau) of Maribavir	91.5 Microgram*hour per milliliter (mcg*h/mL) Interval 79.7 to 105.0	—

PRIMARY outcome

Timeframe: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B

Population: PK set consisted of all participants who received at least 1 dose of investigational product and had evaluable PK data (defined as complete concentration-time profile to obtain meaningful estimates of PK parameters) available for 1 dose regimen.

Lambda z is the first-order rate constant associated with the terminal (log-linear) portion of the plasma concentration versus time curve, determined as the negative slope of the terminal log-linear phase of the curve.

Outcome measures

Measure	Treatment A n=18 Participants Participants received a single 0.5 mg (2 x 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 x 15 mg) oral dose of dextromethorphan tablet on Day 1.	Treatment B n=17 Participants Participants received maribavir 400 mg (2 x 200 mg) tablet orally twice daily from Day 8 to Day 15. On Day 13, participants received a single 0.5 mg (2 × 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 × 15 mg) oral dose of dextromethorphan tablet co-administered with the morning dose of maribavir.
First-order Rate Constant (Lambda z) Associated With the Terminal (Log-linear) Portion of the Curve of Digoxin	0.02 Per hour (/h) Interval 0.02 to 0.02	0.02 Per hour (/h) Interval 0.01 to 0.02

PRIMARY outcome

Timeframe: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B

Population: PK set consisted of all participants who received at least 1 dose of investigational product and had evaluable PK data (defined as complete concentration-time profile to obtain meaningful estimates of PK parameters) available for 1 dose regimen.

Lambda z is the first-order rate constant associated with the terminal (log-linear) portion of the plasma concentration versus time curve, determined as the negative slope of the terminal log-linear phase of the curve.

Outcome measures

Measure	Treatment A n=5 Participants Participants received a single 0.5 mg (2 x 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 x 15 mg) oral dose of dextromethorphan tablet on Day 1.	Treatment B n=5 Participants Participants received maribavir 400 mg (2 x 200 mg) tablet orally twice daily from Day 8 to Day 15. On Day 13, participants received a single 0.5 mg (2 × 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 × 15 mg) oral dose of dextromethorphan tablet co-administered with the morning dose of maribavir.
First-order Rate Constant (Lambda z) Associated With the Terminal (Log-linear) Portion of the Curve of Dextromethorphan Participant 1	0.04 Per hour (/h)	0.04 Per hour (/h)
First-order Rate Constant (Lambda z) Associated With the Terminal (Log-linear) Portion of the Curve of Dextromethorphan Participant 2	0.08 Per hour (/h)	NA Per hour (/h) Terminal phase was not available for this participant.
First-order Rate Constant (Lambda z) Associated With the Terminal (Log-linear) Portion of the Curve of Dextromethorphan Participant 3	NA Per hour (/h) Terminal phase was not available for this participant.	0.11 Per hour (/h)
First-order Rate Constant (Lambda z) Associated With the Terminal (Log-linear) Portion of the Curve of Dextromethorphan Participant 4	0.07 Per hour (/h)	0.08 Per hour (/h)
First-order Rate Constant (Lambda z) Associated With the Terminal (Log-linear) Portion of the Curve of Dextromethorphan Participant 5	0.10 Per hour (/h)	0.12 Per hour (/h)
First-order Rate Constant (Lambda z) Associated With the Terminal (Log-linear) Portion of the Curve of Dextromethorphan Participant 6	0.10 Per hour (/h)	0.10 Per hour (/h)

PRIMARY outcome

Timeframe: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B

Population: PK set consisted of all participants who received at least 1 dose of investigational product and had evaluable PK data (defined as complete concentration-time profile to obtain meaningful estimates of PK parameters) available for 1 dose regimen.

Lambda z is the first-order rate constant associated with the terminal (log-linear) portion of the plasma concentration versus time curve, determined as the negative slope of the terminal log-linear phase of the curve.

Outcome measures

Measure	Treatment A n=18 Participants Participants received a single 0.5 mg (2 x 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 x 15 mg) oral dose of dextromethorphan tablet on Day 1.	Treatment B n=17 Participants Participants received maribavir 400 mg (2 x 200 mg) tablet orally twice daily from Day 8 to Day 15. On Day 13, participants received a single 0.5 mg (2 × 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 × 15 mg) oral dose of dextromethorphan tablet co-administered with the morning dose of maribavir.
First-order Rate Constant (Lambda z) Associated With the Terminal (Log-linear) Portion of the Curve of Dextrorphan	0.16 Per hour (/h) Interval 0.13 to 0.19	0.17 Per hour (/h) Interval 0.14 to 0.2

PRIMARY outcome

Timeframe: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B

Population: PK set consisted of all participants who received at least 1 dose of investigational product and had evaluable PK data (defined as complete concentration-time profile to obtain meaningful estimates of PK parameters) available for 1 dose regimen.

Terminal half-life (t1/2) is the time in hours required for the concentration of the drug to reach half of its original value.

Outcome measures

Measure	Treatment A n=18 Participants Participants received a single 0.5 mg (2 x 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 x 15 mg) oral dose of dextromethorphan tablet on Day 1.	Treatment B n=17 Participants Participants received maribavir 400 mg (2 x 200 mg) tablet orally twice daily from Day 8 to Day 15. On Day 13, participants received a single 0.5 mg (2 × 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 × 15 mg) oral dose of dextromethorphan tablet co-administered with the morning dose of maribavir.
Terminal Half-life (t1/2) of Digoxin	41.5 Hour (h) Interval 38.8 to 44.4	41.8 Hour (h) Interval 36.7 to 47.6

PRIMARY outcome

Timeframe: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B

Population: PK set consisted of all participants who received at least 1 dose of investigational product and had evaluable PK data (defined as complete concentration-time profile to obtain meaningful estimates of PK parameters) available for 1 dose regimen.

Terminal half-life (t1/2) is the time in hours required for the concentration of the drug to reach half of its original value.

Outcome measures

Measure	Treatment A n=5 Participants Participants received a single 0.5 mg (2 x 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 x 15 mg) oral dose of dextromethorphan tablet on Day 1.	Treatment B n=5 Participants Participants received maribavir 400 mg (2 x 200 mg) tablet orally twice daily from Day 8 to Day 15. On Day 13, participants received a single 0.5 mg (2 × 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 × 15 mg) oral dose of dextromethorphan tablet co-administered with the morning dose of maribavir.
Terminal Half-life (t1/2) of Dextromethorphan Participant 1	15.86 Hour (h)	16.17 Hour (h)
Terminal Half-life (t1/2) of Dextromethorphan Participant 2	9.09 Hour (h)	NA Hour (h) Terminal phase was not available for this participant.
Terminal Half-life (t1/2) of Dextromethorphan Participant 3	NA Hour (h) Terminal phase was not available for this participant.	6.43 Hour (h)
Terminal Half-life (t1/2) of Dextromethorphan Participant 4	9.82 Hour (h)	8.72 Hour (h)
Terminal Half-life (t1/2) of Dextromethorphan Participant 5	6.86 Hour (h)	5.58 Hour (h)
Terminal Half-life (t1/2) of Dextromethorphan Participant 6	6.71 Hour (h)	7.03 Hour (h)

PRIMARY outcome

Timeframe: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B

Population: PK set consisted of all participants who received at least 1 dose of investigational product and had evaluable PK data (defined as complete concentration-time profile to obtain meaningful estimates of PK parameters) available for 1 dose regimen.

Terminal half-life (t1/2) is the time in hours required for the concentration of the drug to reach half of its original value.

Outcome measures

Measure	Treatment A n=18 Participants Participants received a single 0.5 mg (2 x 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 x 15 mg) oral dose of dextromethorphan tablet on Day 1.	Treatment B n=17 Participants Participants received maribavir 400 mg (2 x 200 mg) tablet orally twice daily from Day 8 to Day 15. On Day 13, participants received a single 0.5 mg (2 × 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 × 15 mg) oral dose of dextromethorphan tablet co-administered with the morning dose of maribavir.
Terminal Half-life (t1/2) of Dextrorphan	4.42 Hour (h) Interval 3.63 to 5.37	4.16 Hour (h) Interval 3.55 to 4.87

PRIMARY outcome

Timeframe: Pre-dose, 0.25,0.5,1,1.5,2,3,4,5,6,8,12 hours post-dose on Day 13

Population: PK set consisted of all participants who received at least 1 dose of investigational product and had evaluable PK data (defined as complete concentration-time profile to obtain meaningful estimates of PK parameters) available for 1 dose regimen.

Terminal half-life (t1/2) is the time in hours required for the concentration of the drug to reach half of its original value.

Outcome measures

Measure	Treatment A n=17 Participants Participants received a single 0.5 mg (2 x 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 x 15 mg) oral dose of dextromethorphan tablet on Day 1.	Treatment B Participants received maribavir 400 mg (2 x 200 mg) tablet orally twice daily from Day 8 to Day 15. On Day 13, participants received a single 0.5 mg (2 × 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 × 15 mg) oral dose of dextromethorphan tablet co-administered with the morning dose of maribavir.
Terminal Half-life (t1/2) of Maribavir	4.04 Hour (h) Interval 3.66 to 4.46	—

PRIMARY outcome

Timeframe: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B

Population: PK set consisted of all participants who received at least 1 dose of investigational product and had evaluable PK data (defined as complete concentration-time profile to obtain meaningful estimates of PK parameters) available for 1 dose regimen.

CL/F is equal to dose/AUC0-infinity (dose divided by area under the plasma concentration versus time curve extrapolated to infinity [AUC0-infinity]).

Outcome measures

Measure	Treatment A n=18 Participants Participants received a single 0.5 mg (2 x 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 x 15 mg) oral dose of dextromethorphan tablet on Day 1.	Treatment B n=17 Participants Participants received maribavir 400 mg (2 x 200 mg) tablet orally twice daily from Day 8 to Day 15. On Day 13, participants received a single 0.5 mg (2 × 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 × 15 mg) oral dose of dextromethorphan tablet co-administered with the morning dose of maribavir.
Apparent Oral Clearance (CL/F) of Digoxin	15.8 Liter per hour (L/h) Interval 13.4 to 18.6	13.4 Liter per hour (L/h) Interval 11.9 to 15.2

PRIMARY outcome

Timeframe: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B

Population: PK set consisted of all participants who received at least 1 dose of investigational product and had evaluable PK data (defined as complete concentration-time profile to obtain meaningful estimates of PK parameters) available for 1 dose regimen.

CL/F is equal to dose/AUC0-infinity (dose divided by area under the plasma concentration versus time curve extrapolated to infinity [AUC0-infinity])

Outcome measures

Measure	Treatment A n=5 Participants Participants received a single 0.5 mg (2 x 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 x 15 mg) oral dose of dextromethorphan tablet on Day 1.	Treatment B n=5 Participants Participants received maribavir 400 mg (2 x 200 mg) tablet orally twice daily from Day 8 to Day 15. On Day 13, participants received a single 0.5 mg (2 × 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 × 15 mg) oral dose of dextromethorphan tablet co-administered with the morning dose of maribavir.
Apparent Oral Clearance (CL/F) of Dextromethorphan Participant 1	103.19 Liter per hour (L/h)	167.42 Liter per hour (L/h)
Apparent Oral Clearance (CL/F) of Dextromethorphan Participant 2	1067.64 Liter per hour (L/h)	NA Liter per hour (L/h) Terminal phase was not available for this participant.
Apparent Oral Clearance (CL/F) of Dextromethorphan Participant 3	NA Liter per hour (L/h) Terminal phase was not available for this participant.	1193.51 Liter per hour (L/h)
Apparent Oral Clearance (CL/F) of Dextromethorphan Participant 4	177.84 Liter per hour (L/h)	312.65 Liter per hour (L/h)
Apparent Oral Clearance (CL/F) of Dextromethorphan Participant 5	620.71 Liter per hour (L/h)	720.23 Liter per hour (L/h)
Apparent Oral Clearance (CL/F) of Dextromethorphan Participant 6	1119.90 Liter per hour (L/h)	1659.07 Liter per hour (L/h)

PRIMARY outcome

Timeframe: Pre-dose, 0.25,0.5,1,1.5,2,3,4,5,6,8,12 hours post-dose on Day 13

Population: PK set consisted of all participants who received at least 1 dose of investigational product and had evaluable PK data (defined as complete concentration-time profile to obtain meaningful estimates of PK parameters) available for 1 dose regimen.

CL/F is equal to dose/AUCtau (dose divided by area under the curve from time 0 to the end of the dosing interval at steady state [AUCtau])

Outcome measures

Measure	Treatment A n=17 Participants Participants received a single 0.5 mg (2 x 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 x 15 mg) oral dose of dextromethorphan tablet on Day 1.	Treatment B Participants received maribavir 400 mg (2 x 200 mg) tablet orally twice daily from Day 8 to Day 15. On Day 13, participants received a single 0.5 mg (2 × 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 × 15 mg) oral dose of dextromethorphan tablet co-administered with the morning dose of maribavir.
Apparent Oral Clearance (CL/F) of Maribavir	2.19 Liter per hour (L/h) Interval 1.9 to 2.51	—

PRIMARY outcome

Timeframe: Pre-dose, 0.25,0.5,1,1.5,2,3,4,5,6,8,12 hours post-dose on Day 13

Population: PK set consisted of all participants who received at least 1 dose of investigational product and had evaluable PK data (defined as complete concentration-time profile to obtain meaningful estimates of PK parameters) available for 1 dose regimen.

Ctau is the concentration of maribavir at the end of the dosing interval.

Outcome measures

Measure	Treatment A n=17 Participants Participants received a single 0.5 mg (2 x 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 x 15 mg) oral dose of dextromethorphan tablet on Day 1.	Treatment B Participants received maribavir 400 mg (2 x 200 mg) tablet orally twice daily from Day 8 to Day 15. On Day 13, participants received a single 0.5 mg (2 × 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 × 15 mg) oral dose of dextromethorphan tablet co-administered with the morning dose of maribavir.
Concentration at the End of Dosing Interval (Ctau) of Maribavir	2.13 Microgram per milliliter (mcg/mL) Interval 1.66 to 2.73	—

PRIMARY outcome

Timeframe: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B

Population: PK set consisted of all participants who received at least 1 dose of investigational product and had evaluable PK data (defined as complete concentration-time profile to obtain meaningful estimates of PK parameters) available for 1 dose regimen.

Vz/F is the volume of distribution associated with the terminal slope following extravascular administration divided by the fraction of dose absorbed.

Outcome measures

Measure	Treatment A n=18 Participants Participants received a single 0.5 mg (2 x 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 x 15 mg) oral dose of dextromethorphan tablet on Day 1.	Treatment B n=17 Participants Participants received maribavir 400 mg (2 x 200 mg) tablet orally twice daily from Day 8 to Day 15. On Day 13, participants received a single 0.5 mg (2 × 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 × 15 mg) oral dose of dextromethorphan tablet co-administered with the morning dose of maribavir.
Volume of Distribution Divided by the Fraction of Dose Absorbed (Vz/F) of Digoxin	946 Liter (L) Interval 804.0 to 1110.0	809 Liter (L) Interval 723.0 to 906.0

PRIMARY outcome

Timeframe: Pre-dose,0.25,0.5,1,1.5,2,3,4,5,6,8,12,24,48,72 hours post-dose on Day 1 for Treatment A and Day 13 for Treatment B

Population: PK set consisted of all participants who received at least 1 dose of investigational product and had evaluable PK data (defined as complete concentration-time profile to obtain meaningful estimates of PK parameters) available for 1 dose regimen.

Vz/F is the volume of distribution associated with the terminal slope following extravascular administration divided by the fraction of dose absorbed.

Outcome measures

Measure	Treatment A n=5 Participants Participants received a single 0.5 mg (2 x 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 x 15 mg) oral dose of dextromethorphan tablet on Day 1.	Treatment B n=5 Participants Participants received maribavir 400 mg (2 x 200 mg) tablet orally twice daily from Day 8 to Day 15. On Day 13, participants received a single 0.5 mg (2 × 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 × 15 mg) oral dose of dextromethorphan tablet co-administered with the morning dose of maribavir.
Volume of Distribution Divided by the Fraction of Dose Absorbed (Vz/F) of Dextromethorphan Participant 1	2360.54 Liter (L)	3904.44 Liter (L)
Volume of Distribution Divided by the Fraction of Dose Absorbed (Vz/F) of Dextromethorphan Participant 2	14008.68 Liter (L)	NA Liter (L) Terminal phase was not available for this participant.
Volume of Distribution Divided by the Fraction of Dose Absorbed (Vz/F) of Dextromethorphan Participant 3	NA Liter (L) Terminal phase was not available for this participant.	11078.42 Liter (L)
Volume of Distribution Divided by the Fraction of Dose Absorbed (Vz/F) of Dextromethorphan Participant 4	2519.11 Liter (L)	3931.63 Liter (L)
Volume of Distribution Divided by the Fraction of Dose Absorbed (Vz/F) of Dextromethorphan Participant 5	6142.85 Liter (L)	5796.87 Liter (L)
Volume of Distribution Divided by the Fraction of Dose Absorbed (Vz/F) of Dextromethorphan Participant 6	10836.77 Liter (L)	16835.78 Liter (L)

PRIMARY outcome

Timeframe: Pre-dose on Day 13

Population: PK set consisted of all participants who received at least 1 dose of investigational product and had evaluable PK data (defined as complete concentration-time profile to obtain meaningful estimates of PK parameters) available for 1 dose regimen.

C0 is the lowest concentration reached by a drug before the next dose is administered.

Outcome measures

Measure	Treatment A n=17 Participants Participants received a single 0.5 mg (2 x 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 x 15 mg) oral dose of dextromethorphan tablet on Day 1.	Treatment B Participants received maribavir 400 mg (2 x 200 mg) tablet orally twice daily from Day 8 to Day 15. On Day 13, participants received a single 0.5 mg (2 × 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 × 15 mg) oral dose of dextromethorphan tablet co-administered with the morning dose of maribavir.
Pre-dose Concentration (C0) of Maribavir	2.64 Microgram per milliliter (mcg/mL) Interval 1.92 to 3.62	—

SECONDARY outcome

Timeframe: From start of study drug administration up to follow-up (up to 25 days)

Population: Safety set consisted of all participants who were administered at least 1 dose of the test product (maribavir) or to the other investigational products (digoxin and dextrometorphan) and had at least 1 post-dose safety assessment.

An AE was any untoward medical occurrence in a participant administered an investigational product (IP) and that did not necessarily have a causal relationship with this treatment. AE was considered to be study-related if there was any valid reason, even if undetermined or untested, for suspecting a possible cause-and-effect relationship between the IP and the occurrence of the AE. An AE was considered a TEAE if it had a start date on or after the first dose of IP or if it had a start date before the date of the first dose of IP, but increased in intensity on or after the date of the first dose of IP. A serious adverse event (SAE) was any untoward medical occurrence (related either to the test product or to the other IP or not) that at any dose resulted in death; was life-threatening; required or prolongation of hospitalization; resulted in persistent or significant disability/incapacity; was a congenital abnormality/birth defect; was an important medical event.

Outcome measures

Measure	Treatment A n=18 Participants Participants received a single 0.5 mg (2 x 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 x 15 mg) oral dose of dextromethorphan tablet on Day 1.	Treatment B n=17 Participants Participants received maribavir 400 mg (2 x 200 mg) tablet orally twice daily from Day 8 to Day 15. On Day 13, participants received a single 0.5 mg (2 × 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 × 15 mg) oral dose of dextromethorphan tablet co-administered with the morning dose of maribavir.
Number of Participants With Study-related Adverse Events (AEs), Serious Adverse Events (SAEs) and Treatment-emergent Adverse Events (TEAEs) Study related TEAE	4 Participants	12 Participants
Number of Participants With Study-related Adverse Events (AEs), Serious Adverse Events (SAEs) and Treatment-emergent Adverse Events (TEAEs) Serious AE	0 Participants	0 Participants
Number of Participants With Study-related Adverse Events (AEs), Serious Adverse Events (SAEs) and Treatment-emergent Adverse Events (TEAEs) Any TEAE	4 Participants	12 Participants

SECONDARY outcome

Timeframe: Baseline up to Day 16

Population: Safety set consisted of all participants who were administered at least 1 dose of investigational product (maribavir, digoxin, or dextromethorphan) and had at least 1 post-dose safety assessment.

Clinical significance of the changes observed in the safety parameters to be reported as TEAE was interpreted by the investigator.

Outcome measures

Measure	Treatment A n=18 Participants Participants received a single 0.5 mg (2 x 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 x 15 mg) oral dose of dextromethorphan tablet on Day 1.	Treatment B n=17 Participants Participants received maribavir 400 mg (2 x 200 mg) tablet orally twice daily from Day 8 to Day 15. On Day 13, participants received a single 0.5 mg (2 × 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 × 15 mg) oral dose of dextromethorphan tablet co-administered with the morning dose of maribavir.
Number of Participants With Clinically Significant Changes Reported as TEAE in Physical Examination, Vital Signs, 12-lead ECGs, Hematology, Blood Chemistry and Urinalysis Physical examination	0 Participants	0 Participants
Number of Participants With Clinically Significant Changes Reported as TEAE in Physical Examination, Vital Signs, 12-lead ECGs, Hematology, Blood Chemistry and Urinalysis Vital signs	0 Participants	0 Participants
Number of Participants With Clinically Significant Changes Reported as TEAE in Physical Examination, Vital Signs, 12-lead ECGs, Hematology, Blood Chemistry and Urinalysis 12-lead ECGs	0 Participants	0 Participants
Number of Participants With Clinically Significant Changes Reported as TEAE in Physical Examination, Vital Signs, 12-lead ECGs, Hematology, Blood Chemistry and Urinalysis Hematology	0 Participants	0 Participants
Number of Participants With Clinically Significant Changes Reported as TEAE in Physical Examination, Vital Signs, 12-lead ECGs, Hematology, Blood Chemistry and Urinalysis Blood Chemistry	0 Participants	0 Participants
Number of Participants With Clinically Significant Changes Reported as TEAE in Physical Examination, Vital Signs, 12-lead ECGs, Hematology, Blood Chemistry and Urinalysis Urinalysis	0 Participants	0 Participants

Adverse Events

Treatment A

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Treatment B

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Treatment A n=18 participants at risk Participants received a single 0.5 mg (2 x 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 x 15 mg) oral dose of dextromethorphan tablet on Day 1.	Treatment B n=17 participants at risk Participants received maribavir 400 mg (2 x 200 mg) tablet orally twice daily from Day 8 to Day 15. On Day 13, participants received a single 0.5 mg (2 × 0.25 mg) oral dose of digoxin tablet and a single 30 mg (2 × 15 mg) oral dose of dextromethorphan tablet co-administered with the morning dose of maribavir.
Eye disorders Dry eye	5.6% 1/18 • Number of events 1 • From start of study drug administration up to follow-up (up to 25 days)	0.00% 0/17 • From start of study drug administration up to follow-up (up to 25 days)
Eye disorders Vision blurred	0.00% 0/18 • From start of study drug administration up to follow-up (up to 25 days)	11.8% 2/17 • Number of events 2 • From start of study drug administration up to follow-up (up to 25 days)
Gastrointestinal disorders Abdominal discomfort	0.00% 0/18 • From start of study drug administration up to follow-up (up to 25 days)	5.9% 1/17 • Number of events 1 • From start of study drug administration up to follow-up (up to 25 days)
Gastrointestinal disorders Flatulence	11.1% 2/18 • Number of events 2 • From start of study drug administration up to follow-up (up to 25 days)	0.00% 0/17 • From start of study drug administration up to follow-up (up to 25 days)
Gastrointestinal disorders Nausea	0.00% 0/18 • From start of study drug administration up to follow-up (up to 25 days)	5.9% 1/17 • Number of events 1 • From start of study drug administration up to follow-up (up to 25 days)
Nervous system disorders Dysgeusia	0.00% 0/18 • From start of study drug administration up to follow-up (up to 25 days)	41.2% 7/17 • Number of events 8 • From start of study drug administration up to follow-up (up to 25 days)
Nervous system disorders Headache	11.1% 2/18 • Number of events 2 • From start of study drug administration up to follow-up (up to 25 days)	35.3% 6/17 • Number of events 6 • From start of study drug administration up to follow-up (up to 25 days)

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Email: ClinicalTransparency@shire.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER