Study of SHP620 (Maribavir) in Healthy Adults

• Sponsor: Shire (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02775240
• Collaborator: (none)
• Enrollment: 18
• Location: 1
• Arms: 3
• Actual Duration (Months): 1.7
• Patients Per Site Per Month: 10.3

Study Details

Study Description

Brief Summary

The purpose of this study is to determine how an investigational treatment (maribavir) is handled by the body when administered with two already approved drugs (digoxin and dextromethorphan). The study will also look at the safety and tolerability when maribavir is coadministered with digoxin and dextromethorphan versus digoxin and dextromethorphan alone.

Condition or Disease	Intervention/Treatment	Phase
Cytomegalovirus (CMV)	Drug: Digoxin; Drug: Maribavir; Drug: Dextromethorphan	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: A Phase 1, Open-label, 2-period Fixed-sequence Study to Evaluate the Effect of Multiple Doses of SHP620 (Maribavir) on the Pharmacokinetics of Digoxin and Dextromethorphan in Healthy Adult Subjects
• Actual Study Start Date: Jul 21, 2016
• Actual Primary Completion Date: Sep 12, 2016
• Actual Study Completion Date: Sep 12, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Digoxin On Day 1, subjects will receive a single 0.5 mg (2 x 0.25 mg) oral dose of digoxin.	Drug: Digoxin; 0.5 mg (2 x 0.25 mg) Digoxin oral dose
Experimental: Maribavir On Day 8 through Day 15, subjects will receive a 400 mg (2 x 200 mg) BID oral dose of maribavir. Subjects will be given the second dose of maribavir approximately 12 hours after the first dose. On Day 13, subjects will receive a coadministration of a single 0.5 mg (2 x 0.25 mg) oral dose of digoxin and a single 30 mg oral dose of dextromethorphan given with the morning dose of maribavir.	Drug: Digoxin; 0.5 mg (2 x 0.25 mg) Digoxin oral dose; Drug: Maribavir; 200mg twice a day for 8 days; Drug: Dextromethorphan; 30 mg oral dose
Active Comparator: Dextromethorphan On Day 1, subjects will receive a single 30 mg oral dose of dextromethorphan.	Drug: Dextromethorphan; 30 mg oral dose

Outcome Measures

Primary Outcome Measures

1. Maximum Observed Plasma Concentration (Cmax) of Digoxin [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]

   Cmax is the maximum observed plasma concentration of digoxin.

2. Maximum Observed Plasma Concentration (Cmax) of Dextromethorphan [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]

   Cmax is the maximum observed plasma concentration of dextromethorphan.

3. Maximum Observed Plasma Concentration (Cmax) of Dextrorphan [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]

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

4. Maximum Observed Plasma Concentration (Cmax) of Maribavir [Pre-dose, 0.25,0.5,1,1.5,2,3,4,5,6,8,12 hours post-dose on Day 13]

   Cmax is the maximum observed plasma concentration of maribavir.

5. Time to Reach Maximum Plasma Concentration (Tmax) of Digoxin [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]

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

6. Time to Reach Maximum Plasma Concentration (Tmax) of Dextromethorphan [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]

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

7. Time to Reach Maximum Plasma Concentration (Tmax) of Dextrorphan [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]

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

8. Time to Reach Maximum Plasma Concentration (Tmax) of Maribavir [Pre-dose, 0.25,0.5,1,1.5,2,3,4,5,6,8,12 hours post-dose on Day 13]

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

9. Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Digoxin [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]

   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.

10. Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Dextromethorphan [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]

    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.

11. Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Dextrorphan [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]

    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.

12. Area Under the Plasma Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) of Digoxin [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]

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

13. Area Under the Plasma Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) of Dextromethorphan [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]

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

14. Area Under the Plasma Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) of Dextrorphan [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]

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

15. 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) [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]

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

16. 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) [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]

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

17. Area Under the Plasma Concentration Versus Time Curve From Time Zero to the End of the Dosing Interval at Steady-State (AUCtau) of Maribavir [Pre-dose, 0.25,0.5,1,1.5,2,3,4,5,6,8,12 hours post-dose on Day 13]

    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.

18. First-order Rate Constant (Lambda z) Associated With the Terminal (Log-linear) Portion of the Curve of Digoxin [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]

    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.

19. First-order Rate Constant (Lambda z) Associated With the Terminal (Log-linear) Portion of the Curve of Dextromethorphan [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]

    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.

20. First-order Rate Constant (Lambda z) Associated With the Terminal (Log-linear) Portion of the Curve of Dextrorphan [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]

    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.

21. Terminal Half-life (t1/2) of Digoxin [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]

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

22. Terminal Half-life (t1/2) of Dextromethorphan [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]

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

23. Terminal Half-life (t1/2) of Dextrorphan [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]

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

24. Terminal Half-life (t1/2) of Maribavir [Pre-dose, 0.25,0.5,1,1.5,2,3,4,5,6,8,12 hours post-dose on Day 13]

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

25. Apparent Oral Clearance (CL/F) of Digoxin [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]

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

26. Apparent Oral Clearance (CL/F) of Dextromethorphan [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]

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

27. Apparent Oral Clearance (CL/F) of Maribavir [Pre-dose, 0.25,0.5,1,1.5,2,3,4,5,6,8,12 hours post-dose on Day 13]

    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])

28. Concentration at the End of Dosing Interval (Ctau) of Maribavir [Pre-dose, 0.25,0.5,1,1.5,2,3,4,5,6,8,12 hours post-dose on Day 13]

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

29. Volume of Distribution Divided by the Fraction of Dose Absorbed (Vz/F) of Digoxin [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]

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

30. Volume of Distribution Divided by the Fraction of Dose Absorbed (Vz/F) of Dextromethorphan [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]

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

31. Pre-dose Concentration (C0) of Maribavir [Pre-dose on Day 13]

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

Secondary Outcome Measures

1. Number of Participants With Study-related Adverse Events (AEs), Serious Adverse Events (SAEs) and Treatment-emergent Adverse Events (TEAEs) [From start of study drug administration up to follow-up (up to 25 days)]

   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.

2. Number of Participants With Clinically Significant Changes Reported as TEAE in Physical Examination, Vital Signs, 12-lead ECGs, Hematology, Blood Chemistry and Urinalysis [Baseline up to Day 16]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• An understanding, ability, and willingness to fully comply with study procedures and restrictions.

• Ability to provide written, personally signed, and dated informed consent to participate in the study, before completing any study-related procedures.

• Age 18-50 years, inclusive at the time of consent.

• Subjects must be willing to consent to and provide blood samples for pharmacogenomics analysis.

• Willingness to comply with any applicable contraceptive requirements of the protocol and is:

1. Male, or

2. Female of non-childbearing potential

3. Non-pregnant, non-lactating female

4. Females must be at least 90 days postpartum or nulliparous.

• Must be considered "healthy." Healthy status is defined by absence of evidence of any active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead ECG, hematology, blood chemistry (includes T3, T4, and TSH at screening only), and urinalysis.

• Body mass index (BMI) between 18.5 and 30.0 kg/m2 inclusive.

• Hemoglobin is equal to or greater than 12.0g/dL.

• Ability to swallow a dose of investigational product (which may be multiple tablets at one time or consecutively 1 tablet at a time)

Exclusion Criteria:

• Subject has a clinically significant history or a disorder detected during the medical interview/physical examination such as any cardiovascular, broncho-pulmonary, gastrointestinal (eg, inflammatory bowel disease, chronic diarrhea), hepatic, biliary (including gallbladder removal), renal, hematological, endocrine, autoimmune, neurological, or psychiatric disease (including depression) or any other medical condition that is capable of altering the absorption, metabolism, or elimination of drugs; or of constituting a risk factor when taking the investigational product in the judgment of the investigator.

• Known or suspected intolerance or hypersensitivity to the investigational product(s), closely related compounds, or any of the stated ingredients.

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

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

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

• Within 30 days prior to the first dose of investigational product:

1. Have used an investigational product (if elimination half-life is <6 days, otherwise 5 half-lives).

2. Have been enrolled in a clinical study (including vaccine studies) that, in the investigator's opinion, may impact this study.

3. Have had any substantial changes in eating habits, as assessed by the investigator.

• Confirmed systolic blood pressure >139 mmHg or <89 mmHg and diastolic blood pressure

89 mmHg or <49 mmHg.

• Twelve-lead ECG demonstrating QTcB >450 msec at screening.

• A positive screen for alcohol or drugs of abuse at screening or Day -1, Period 1.

• Male subjects who consume more than 21 units of alcohol per week or 3 units per day; female subjects who consume more than 14 units of alcohol per week or 2 units per day (1 alcohol unit=1 beer or 1 wine [5 oz/150 mL] or 1 liquor [1.5 oz/40 mL] or 0.75 oz alcohol).

• A positive human immunodeficiency virus, hepatitis B surface antibody, or hepatitis C virus antibody screen.

• Use of tobacco in any form (eg, smoking or chewing) or other nicotine-containing products in any form (eg, gum, patch). Ex-users must report that they have stopped using tobacco for at least 30 days prior to receiving the first dose of investigational product.

• Routine consumption of more than 2 units of caffeine per day or subjects who experience caffeine withdrawal headaches. (One caffeine unit is contained in the following items: one 6 oz [180 mL] cup of coffee, two 12 oz [360 mL] cans of cola, one 12 oz cup of tea, or three 1 oz [85 g] chocolate bars. Decaffeinated coffee, tea, or cola are not considered to contain caffeine.)

• Prior screen failure, randomization, participation, or enrollment in this study or prior enrollment in a clinical study investigating maribavir.

• Current use (defined as use within 14 days prior to the first dose of investigational product) of any medication (including over-the-counter, herbal, or homeopathic preparations [eg, St. John's wort, ginkgo biloba]) with the exception of hormonal replacement therapy and occasional use of ibuprofen and acetaminophen.

• History of sensitivity to heparin or heparin-induced thrombocytopenia.

• Ingestion of known CYP3A modulators within 7 days of Day 1, Period 1 (includes grapefruit or grapefruit juice, oranges, Seville oranges, apples or apple juice, vegetables from the mustard green family [eg, kale, broccoli, watercress, collard greens, kohlrabi, Brussels sprouts, mustard], charbroiled meats, and products containing these ingredients).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Pharmacology of Miami, Inc.	Miami	Florida	United States	33014

Sponsors and Collaborators

• Shire

Investigators

• Study Director: Study Director, Takeda

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Shire
• ClinicalTrials.gov Identifier: NCT02775240
• Other Study ID Numbers: SHP620-115
• First Posted: May 17, 2016
• Last Update Posted: Jun 3, 2021
• Last Verified: May 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Shire: Maribavir
• Additional relevant MeSH terms: Cytomegalovirus Infections; Maribavir; Digoxin; Dextromethorphan

Study Results

Participant Flow

Recruitment Details	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).
Pre-assignment Detail	A total of 18 participants were screened and were enrolled in the study and received the treatment.

Arm/Group Title	Treatment A and B
Arm/Group Description	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.
Period Title: Overall Study
STARTED	18
Started Treatment A	18
Started Treatment B	17
COMPLETED	17
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Treatment A and B
Arm/Group Description	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 Participants	18
Age (Year) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Year]	38.1 (8.72)
Sex: Female, Male (Count of Participants)
Female	7 38.9%
Male	11 61.1%

Outcome Measures

1. Primary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) of Digoxin
Description	Cmax is the maximum observed plasma concentration of digoxin.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	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.	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.
Measure Participants	18	17
Geometric Mean (95% Confidence Interval) [Nanogram per milliliter (ng/mL)]	1.94	2.35

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment A, Treatment B
	Comments	Comparison of Treatment B over Treatment A for Cmax of Digoxin
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	1.248
	Confidence Interval	(2-Sided) 90%; 1.130 to 1.378
	Parameter Dispersion	Type: Value:
	Estimation Comments	Log-transformed Cmax values were compared between treatment regimens using a linear mixed effects model with treatment regimen as fixed effect and participant as random effect.

2. Primary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) of Dextromethorphan
Description	Cmax is the maximum observed plasma concentration of dextromethorphan.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	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.	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.
Measure Participants	18	17
Geometric Mean (95% Confidence Interval) [Nanogram per milliliter (ng/mL)]	1.14	1.14

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment A, Treatment B
	Comments	Comparison of Treatment B over Treatment A for Cmax of Dextromethorphan
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	0.944
	Confidence Interval	(2-Sided) 90%; 0.778 to 1.144
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) of Dextrorphan
Description	Cmax is the maximum observed plasma concentration of dextrorphan, the metabolite of dextromethorphan.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	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.	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.
Measure Participants	18	17
Geometric Mean (95% Confidence Interval) [Nanogram per milliliter (ng/mL)]	433	401

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment A, Treatment B
	Comments	Comparison of Treatment B over Treatment A for Cmax of Dextrorphan
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	0.943
	Confidence Interval	(2-Sided) 90%; 0.883 to 1.007
	Parameter Dispersion	Type: Value:
	Estimation Comments	Log-transformed Cmax values were compared between treatment regimens using a linear mixed effects model with treatment regimen as fixed effect and participant as random effect.

4. Primary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) of Maribavir
Description	Cmax is the maximum observed plasma concentration of maribavir.
Time Frame	Pre-dose, 0.25,0.5,1,1.5,2,3,4,5,6,8,12 hours post-dose on Day 13

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment B
Arm/Group Description	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.
Measure Participants	17
Geometric Mean (95% Confidence Interval) [Microgram per milliliter (mcg/mL)]	17.6

5. Primary Outcome

Title	Time to Reach Maximum Plasma Concentration (Tmax) of Digoxin
Description	Tmax is the time to reach the maximum observed drug concentration in plasma during a dosing interval.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	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.	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.
Measure Participants	18	17
Median (Full Range) [Hour (h)]	1.00	1.00

6. Primary Outcome

Title	Time to Reach Maximum Plasma Concentration (Tmax) of Dextromethorphan
Description	Tmax is the time to reach the maximum observed drug concentration in plasma during a dosing interval.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	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.	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.
Measure Participants	18	17
Median (Full Range) [Hour (h)]	3.00	3.00

7. Primary Outcome

Title	Time to Reach Maximum Plasma Concentration (Tmax) of Dextrorphan
Description	Tmax is the time to reach the maximum observed drug concentration in plasma during a dosing interval.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	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.	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.
Measure Participants	18	17
Median (Full Range) [Hour (h)]	2.00	2.00

8. Primary Outcome

Title	Time to Reach Maximum Plasma Concentration (Tmax) of Maribavir
Description	Tmax is the time to reach the maximum observed drug concentration in plasma during a dosing interval.
Time Frame	Pre-dose, 0.25,0.5,1,1.5,2,3,4,5,6,8,12 hours post-dose on Day 13

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment B
Arm/Group Description	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.
Measure Participants	17
Median (Full Range) [Hour (h)]	2.00

9. Primary Outcome

Title	Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Digoxin
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	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.	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.
Measure Participants	18	17
Geometric Mean (95% Confidence Interval) [Nanogram*hour per milliliter (ng*h/mL)]	31.6	37.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment A, Treatment B
	Comments	Comparison of Treatment B over Treatment A for AUC0-infinity of Digoxin
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	1.206
	Confidence Interval	(2-Sided) 90%; 1.099 to 1.324
	Parameter Dispersion	Type: Value:
	Estimation Comments	Log-transformed AUC0-infinity values were compared between treatment regimens using a linear mixed effects model with treatment regimen as fixed effect and participant as random effect.

10. Primary Outcome

Title	Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Dextromethorphan
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	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.	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.
Measure Participants	5	5
Participant 1	290.74	179.19
Participant 2	28.10	NA
Participant 3	NA	25.14
Participant 4	168.69	95.95
Participant 5	48.33	41.65
Participant 6	26.79	18.08

11. Primary Outcome

Title	Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Dextrorphan
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	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.	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.
Measure Participants	18	17
Geometric Mean (95% Confidence Interval) [Nanogram*hour per milliliter (ng*h/mL)]	2270	2150

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment A, Treatment B
	Comments	Comparison of Treatment B over Treatment A for AUC0-infinity of Dextrorphan
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	0.971
	Confidence Interval	(2-Sided) 90%; 0.943 to 0.999
	Parameter Dispersion	Type: Value:
	Estimation Comments	Log-transformed AUC0-infinity values were compared between treatment regimens using a linear mixed effects model with treatment regimen as fixed effect and participant as random effect.

12. Primary Outcome

Title	Area Under the Plasma Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) of Digoxin
Description	AUClast is the area under the plasma concentration versus time curve from the time of dosing to the last measurable concentration.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	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.	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.
Measure Participants	18	17
Geometric Mean (95% Confidence Interval) [Nanogram*hour per milliliter (ng*h/mL)]	23.0	26.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment A, Treatment B
	Comments	Comparison of Treatment B over Treatment A for AUClast for Digoxin
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	1.179
	Confidence Interval	(2-Sided) 90%; 1.080 to 1.287
	Parameter Dispersion	Type: Value:
	Estimation Comments	Log-transformed AUClast values were compared between treatment regimens using a linear mixed effects model with treatment regimen as fixed effect and participant as random effect.

13. Primary Outcome

Title	Area Under the Plasma Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) of Dextromethorphan
Description	AUClast is the area under the plasma concentration versus time curve from the time of dosing to the last measurable concentration.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	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.	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.
Measure Participants	18	17
Geometric Mean (95% Confidence Interval) [Nanogram*hour per milliliter (ng*h/mL)]	7.06	6.77

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment A, Treatment B
	Comments	Comparison of Treatment B over Treatment A for AUClast of Dextromethorphan
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	0.882
	Confidence Interval	(2-Sided) 90%; 0.696 to 1.118
	Parameter Dispersion	Type: Value:
	Estimation Comments	Log-transformed AUClast values were compared between treatment regimens using a linear mixed effects model with treatment regimen as fixed effect and participant as random effect.

14. Primary Outcome

Title	Area Under the Plasma Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) of Dextrorphan
Description	AUClast is the area under the plasma concentration versus time curve from the time of dosing to the last measurable concentration.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	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.	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.
Measure Participants	18	17
Geometric Mean (95% Confidence Interval) [Nanogram*hour per milliliter (ng*h/mL)]	2200	2110

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment A, Treatment B
	Comments	Comparison of Treatment B over Treatment A for AUClast for Dextrorphan
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	0.973
	Confidence Interval	(2-Sided) 90%; 0.949 to 0.998
	Parameter Dispersion	Type: Value:
	Estimation Comments	Log-transformed AUClast values were compared between treatment regimens using a linear mixed effects model with treatment regimen as fixed effect and participant as random effect.

15. Primary Outcome

Title	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)
Description	AUClast parent/metabolite ratio is the ratio of AUClast for dextromethorphan over AUClast for dextrorphan.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	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.	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.
Measure Participants	18	17
Geometric Mean (95% Confidence Interval) [Ratio of AUClast]	0.003	0.003

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment A, Treatment B
	Comments	Comparison of Treatment B over Treatment A for Dextromethorphan/Dextrorphan (Parent/Metabolite) AUClast ratio
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	0.905
	Confidence Interval	(2-Sided) 90%; 0.721 to 1.138
	Parameter Dispersion	Type: Value:
	Estimation Comments	Log-transformed AUClast ratio values were compared between treatment regimens using a linear mixed effects model with treatment regimen as fixed effect and participant as random effect.

16. Primary Outcome

Title	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)
Description	AUC0-infinity parent/metabolite ratio is the ratio of AUC0-infinity for dextromethorphan over AUC0-infinity for dextrorphan.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	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.	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.
Measure Participants	5	5
Participant 1	0.177	0.127
Participant 2	0.009	NA
Participant 3	NA	0.014
Participant 4	0.096	0.056
Participant 5	0.028	0.025
Participant 6	0.013	0.008

17. Primary Outcome

Title	Area Under the Plasma Concentration Versus Time Curve From Time Zero to the End of the Dosing Interval at Steady-State (AUCtau) of Maribavir
Description	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.
Time Frame	Pre-dose, 0.25,0.5,1,1.5,2,3,4,5,6,8,12 hours post-dose on Day 13

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment B
Arm/Group Description	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.
Measure Participants	17
Geometric Mean (95% Confidence Interval) [Microgram*hour per milliliter (mcg*h/mL)]	91.5

18. Primary Outcome

Title	First-order Rate Constant (Lambda z) Associated With the Terminal (Log-linear) Portion of the Curve of Digoxin
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	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.	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.
Measure Participants	18	17
Geometric Mean (95% Confidence Interval) [Per hour (/h)]	0.02	0.02

19. Primary Outcome

Title	First-order Rate Constant (Lambda z) Associated With the Terminal (Log-linear) Portion of the Curve of Dextromethorphan
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	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.	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.
Measure Participants	5	5
Participant 1	0.04	0.04
Participant 2	0.08	NA
Participant 3	NA	0.11
Participant 4	0.07	0.08
Participant 5	0.10	0.12
Participant 6	0.10	0.10

20. Primary Outcome

Title	First-order Rate Constant (Lambda z) Associated With the Terminal (Log-linear) Portion of the Curve of Dextrorphan
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	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.	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.
Measure Participants	18	17
Geometric Mean (95% Confidence Interval) [Per hour (/h)]	0.16	0.17

21. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	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.	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.
Measure Participants	18	17
Geometric Mean (95% Confidence Interval) [Hour (h)]	41.5	41.8

22. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	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.	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.
Measure Participants	5	5
Participant 1	15.86	16.17
Participant 2	9.09	NA
Participant 3	NA	6.43
Participant 4	9.82	8.72
Participant 5	6.86	5.58
Participant 6	6.71	7.03

23. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	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.	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.
Measure Participants	18	17
Geometric Mean (95% Confidence Interval) [Hour (h)]	4.42	4.16

24. Primary Outcome

Title	Terminal Half-life (t1/2) of Maribavir
Description	Terminal half-life (t1/2) is the time in hours required for the concentration of the drug to reach half of its original value.
Time Frame	Pre-dose, 0.25,0.5,1,1.5,2,3,4,5,6,8,12 hours post-dose on Day 13

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment B
Arm/Group Description	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.
Measure Participants	17
Geometric Mean (95% Confidence Interval) [Hour (h)]	4.04

25. Primary Outcome

Title	Apparent Oral Clearance (CL/F) of Digoxin
Description	CL/F is equal to dose/AUC0-infinity (dose divided by area under the plasma concentration versus time curve extrapolated to infinity [AUC0-infinity]).
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	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.	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.
Measure Participants	18	17
Geometric Mean (95% Confidence Interval) [Liter per hour (L/h)]	15.8	13.4

26. Primary Outcome

Title	Apparent Oral Clearance (CL/F) of Dextromethorphan
Description	CL/F is equal to dose/AUC0-infinity (dose divided by area under the plasma concentration versus time curve extrapolated to infinity [AUC0-infinity])
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	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.	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.
Measure Participants	5	5
Participant 1	103.19	167.42
Participant 2	1067.64	NA
Participant 3	NA	1193.51
Participant 4	177.84	312.65
Participant 5	620.71	720.23
Participant 6	1119.90	1659.07

27. Primary Outcome

Title	Apparent Oral Clearance (CL/F) of Maribavir
Description	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])
Time Frame	Pre-dose, 0.25,0.5,1,1.5,2,3,4,5,6,8,12 hours post-dose on Day 13

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment B
Arm/Group Description	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.
Measure Participants	17
Geometric Mean (95% Confidence Interval) [Liter per hour (L/h)]	2.19

28. Primary Outcome

Title	Concentration at the End of Dosing Interval (Ctau) of Maribavir
Description	Ctau is the concentration of maribavir at the end of the dosing interval.
Time Frame	Pre-dose, 0.25,0.5,1,1.5,2,3,4,5,6,8,12 hours post-dose on Day 13

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment B
Arm/Group Description	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.
Measure Participants	17
Geometric Mean (95% Confidence Interval) [Microgram per milliliter (mcg/mL)]	2.13

29. Primary Outcome

Title	Volume of Distribution Divided by the Fraction of Dose Absorbed (Vz/F) of Digoxin
Description	Vz/F is the volume of distribution associated with the terminal slope following extravascular administration divided by the fraction of dose absorbed.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	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.	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.
Measure Participants	18	17
Geometric Mean (95% Confidence Interval) [Liter (L)]	946	809

30. Primary Outcome

Title	Volume of Distribution Divided by the Fraction of Dose Absorbed (Vz/F) of Dextromethorphan
Description	Vz/F is the volume of distribution associated with the terminal slope following extravascular administration divided by the fraction of dose absorbed.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	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.	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.
Measure Participants	5	5
Participant 1	2360.54	3904.44
Participant 2	14008.68	NA
Participant 3	NA	11078.42
Participant 4	2519.11	3931.63
Participant 5	6142.85	5796.87
Participant 6	10836.77	16835.78

31. Primary Outcome

Title	Pre-dose Concentration (C0) of Maribavir
Description	C0 is the lowest concentration reached by a drug before the next dose is administered.
Time Frame	Pre-dose on Day 13

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment B
Arm/Group Description	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.
Measure Participants	17
Geometric Mean (95% Confidence Interval) [Microgram per milliliter (mcg/mL)]	2.64

32. Secondary Outcome

Title	Number of Participants With Study-related Adverse Events (AEs), Serious Adverse Events (SAEs) and Treatment-emergent Adverse Events (TEAEs)
Description	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.
Time Frame	From start of study drug administration up to follow-up (up to 25 days)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	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.	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.
Measure Participants	18	17
Study related TEAE	4 22.2%	12 NaN
Serious AE	0 0%	0 NaN
Any TEAE	4 22.2%	12 NaN

33. Secondary Outcome

Title	Number of Participants With Clinically Significant Changes Reported as TEAE in Physical Examination, Vital Signs, 12-lead ECGs, Hematology, Blood Chemistry and Urinalysis
Description	Clinical significance of the changes observed in the safety parameters to be reported as TEAE was interpreted by the investigator.
Time Frame	Baseline up to Day 16

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	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.	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.
Measure Participants	18	17
Physical examination	0 0%	0 NaN
Vital signs	0 0%	0 NaN
12-lead ECGs	0 0%	0 NaN
Hematology	0 0%	0 NaN
Blood Chemistry	0 0%	0 NaN
Urinalysis	0 0%	0 NaN

Adverse Events

Time Frame	From start of study drug administration up to follow-up (up to 25 days)
Arm/Group Title	Treatment A		Treatment B
Arm/Group Description	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.		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.
All Cause Mortality
	Treatment A		Treatment B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/17 (0%)
Serious Adverse Events
	Treatment A		Treatment B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/17 (0%)
Other (Not Including Serious) Adverse Events
	Treatment A		Treatment B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/18 (22.2%)		12/17 (70.6%)
Eye disorders
Dry eye	1/18 (5.6%)	1	0/17 (0%)	0
Vision blurred	0/18 (0%)	0	2/17 (11.8%)	2
Gastrointestinal disorders
Abdominal discomfort	0/18 (0%)	0	1/17 (5.9%)	1
Flatulence	2/18 (11.1%)	2	0/17 (0%)	0
Nausea	0/18 (0%)	0	1/17 (5.9%)	1
Nervous system disorders
Dysgeusia	0/18 (0%)	0	7/17 (41.2%)	8
Headache	2/18 (11.1%)	2	6/17 (35.3%)	6

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.