Cytomegalovirus (CMV)
Conditions
Keywords
Maribavir
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.
Interventions
DRUGDigoxin
0.5 mg (2 x 0.25 mg) Digoxin oral dose
DRUGMaribavir
200mg twice a day for 8 days
DRUGDextromethorphan
30 mg oral dose
Sponsors
Shire
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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 \[AUC0-infinity\]). |
| 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 \[AUC0-infinity\]) |
| 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 \[AUCtau\]) |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Countries
United States
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 details
A total of 18 participants were screened and were enrolled in the study and received the treatment.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 18 |
| Total | 18 |
Baseline characteristics
| Characteristic | Treatment A and B |
|---|---|
| Age, Continuous | 38.1 Year STANDARD_DEVIATION 8.72 |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 17 |
| other Total, other adverse events | 4 / 18 | 12 / 17 |
| serious Total, serious adverse events | 0 / 18 | 0 / 17 |
Outcome results
Primary
Apparent Oral Clearance (CL/F) of Dextromethorphan
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
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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A | Apparent Oral Clearance (CL/F) of Dextromethorphan | Participant 4 | 177.84 Liter per hour (L/h) |
| Treatment A | Apparent Oral Clearance (CL/F) of Dextromethorphan | Participant 1 | 103.19 Liter per hour (L/h) |
| Treatment A | Apparent Oral Clearance (CL/F) of Dextromethorphan | Participant 5 | 620.71 Liter per hour (L/h) |
| Treatment A | Apparent Oral Clearance (CL/F) of Dextromethorphan | Participant 3 | NA Liter per hour (L/h) |
| Treatment A | Apparent Oral Clearance (CL/F) of Dextromethorphan | Participant 6 | 1119.90 Liter per hour (L/h) |
| Treatment A | Apparent Oral Clearance (CL/F) of Dextromethorphan | Participant 2 | 1067.64 Liter per hour (L/h) |
| Treatment B | Apparent Oral Clearance (CL/F) of Dextromethorphan | Participant 6 | 1659.07 Liter per hour (L/h) |
| Treatment B | Apparent Oral Clearance (CL/F) of Dextromethorphan | Participant 2 | NA Liter per hour (L/h) |
| Treatment B | Apparent Oral Clearance (CL/F) of Dextromethorphan | Participant 3 | 1193.51 Liter per hour (L/h) |
| Treatment B | Apparent Oral Clearance (CL/F) of Dextromethorphan | Participant 4 | 312.65 Liter per hour (L/h) |
| Treatment B | Apparent Oral Clearance (CL/F) of Dextromethorphan | Participant 5 | 720.23 Liter per hour (L/h) |
| Treatment B | Apparent Oral Clearance (CL/F) of Dextromethorphan | Participant 1 | 167.42 Liter per hour (L/h) |
Primary
Apparent Oral Clearance (CL/F) of Digoxin
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
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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Treatment A | Apparent Oral Clearance (CL/F) of Digoxin | 15.8 Liter per hour (L/h) |
| Treatment B | Apparent Oral Clearance (CL/F) of Digoxin | 13.4 Liter per hour (L/h) |
Primary
Apparent Oral Clearance (CL/F) of Maribavir
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
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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Treatment A | Apparent Oral Clearance (CL/F) of Maribavir | 2.19 Liter per hour (L/h) |
Primary
Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Dextromethorphan
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
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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A | 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) |
| Treatment A | 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) |
| Treatment A | 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) |
| Treatment A | 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) |
| Treatment A | 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) |
| Treatment A | 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) |
| Treatment B | Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Dextromethorphan | Participant 5 | 41.65 Nanogram*hour per milliliter (ng*h/mL) |
| Treatment B | Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Dextromethorphan | Participant 1 | 179.19 Nanogram*hour per milliliter (ng*h/mL) |
| Treatment B | Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Dextromethorphan | Participant 4 | 95.95 Nanogram*hour per milliliter (ng*h/mL) |
| Treatment B | Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Dextromethorphan | Participant 2 | NA Nanogram*hour per milliliter (ng*h/mL) |
| Treatment B | Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Dextromethorphan | Participant 6 | 18.08 Nanogram*hour per milliliter (ng*h/mL) |
| Treatment B | Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Dextromethorphan | Participant 3 | 25.14 Nanogram*hour per milliliter (ng*h/mL) |
Primary
Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Dextrorphan
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
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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Treatment A | Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Dextrorphan | 2270 Nanogram*hour per milliliter (ng*h/mL) |
| Treatment B | Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Dextrorphan | 2150 Nanogram*hour per milliliter (ng*h/mL) |
Comparison: Comparison of Treatment B over Treatment A for AUC0-infinity of Dextrorphan90% CI: [0.943, 0.999]Linear mixed effects model
Primary
Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Digoxin
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
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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Treatment A | Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Digoxin | 31.6 Nanogram*hour per milliliter (ng*h/mL) |
| Treatment B | Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Digoxin | 37.3 Nanogram*hour per milliliter (ng*h/mL) |
Comparison: Comparison of Treatment B over Treatment A for AUC0-infinity of Digoxin90% CI: [1.099, 1.324]Linear mixed effects model
Primary
Area Under the Plasma Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) of Dextromethorphan
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
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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Treatment A | 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) |
| Treatment B | Area Under the Plasma Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) of Dextromethorphan | 6.77 Nanogram*hour per milliliter (ng*h/mL) |
Comparison: Comparison of Treatment B over Treatment A for AUClast of Dextromethorphan90% CI: [0.696, 1.118]Linear mixed effects model
Primary
Area Under the Plasma Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) of Dextrorphan
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
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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Treatment A | 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) |
| Treatment B | Area Under the Plasma Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) of Dextrorphan | 2110 Nanogram*hour per milliliter (ng*h/mL) |
Comparison: Comparison of Treatment B over Treatment A for AUClast for Dextrorphan90% CI: [0.949, 0.998]Linear mixed effects model
Primary
Area Under the Plasma Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) of Digoxin
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
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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Treatment A | 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) |
| Treatment B | Area Under the Plasma Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) of Digoxin | 26.7 Nanogram*hour per milliliter (ng*h/mL) |
Comparison: Comparison of Treatment B over Treatment A for AUClast for Digoxin90% CI: [1.08, 1.287]Linear mixed effects model
Primary
Area Under the Plasma Concentration Versus Time Curve From Time Zero to the End of the Dosing Interval at Steady-State (AUCtau) of Maribavir
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
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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Treatment A | 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) |
Primary
Concentration at the End of Dosing Interval (Ctau) of Maribavir
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
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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Treatment A | Concentration at the End of Dosing Interval (Ctau) of Maribavir | 2.13 Microgram per milliliter (mcg/mL) |
Primary
First-order Rate Constant (Lambda z) Associated With the Terminal (Log-linear) Portion of the Curve of Dextromethorphan
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
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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A | 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) |
| Treatment A | 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) |
| Treatment A | First-order Rate Constant (Lambda z) Associated With the Terminal (Log-linear) Portion of the Curve of Dextromethorphan | Participant 3 | NA Per hour (/h) |
| Treatment A | 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) |
| Treatment A | 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) |
| Treatment A | 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) |
| Treatment B | First-order Rate Constant (Lambda z) Associated With the Terminal (Log-linear) Portion of the Curve of Dextromethorphan | Participant 5 | 0.12 Per hour (/h) |
| Treatment B | 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) |
| Treatment B | First-order Rate Constant (Lambda z) Associated With the Terminal (Log-linear) Portion of the Curve of Dextromethorphan | Participant 4 | 0.08 Per hour (/h) |
| Treatment B | First-order Rate Constant (Lambda z) Associated With the Terminal (Log-linear) Portion of the Curve of Dextromethorphan | Participant 2 | NA Per hour (/h) |
| Treatment B | 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) |
| Treatment B | First-order Rate Constant (Lambda z) Associated With the Terminal (Log-linear) Portion of the Curve of Dextromethorphan | Participant 3 | 0.11 Per hour (/h) |
Primary
First-order Rate Constant (Lambda z) Associated With the Terminal (Log-linear) Portion of the Curve of Dextrorphan
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
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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Treatment A | First-order Rate Constant (Lambda z) Associated With the Terminal (Log-linear) Portion of the Curve of Dextrorphan | 0.16 Per hour (/h) |
| Treatment B | First-order Rate Constant (Lambda z) Associated With the Terminal (Log-linear) Portion of the Curve of Dextrorphan | 0.17 Per hour (/h) |
Primary
First-order Rate Constant (Lambda z) Associated With the Terminal (Log-linear) Portion of the Curve of Digoxin
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
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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Treatment A | First-order Rate Constant (Lambda z) Associated With the Terminal (Log-linear) Portion of the Curve of Digoxin | 0.02 Per hour (/h) |
| Treatment B | First-order Rate Constant (Lambda z) Associated With the Terminal (Log-linear) Portion of the Curve of Digoxin | 0.02 Per hour (/h) |
Primary
Maximum Observed Plasma Concentration (Cmax) of Dextromethorphan
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
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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Treatment A | Maximum Observed Plasma Concentration (Cmax) of Dextromethorphan | 1.14 Nanogram per milliliter (ng/mL) |
| Treatment B | Maximum Observed Plasma Concentration (Cmax) of Dextromethorphan | 1.14 Nanogram per milliliter (ng/mL) |
Comparison: Comparison of Treatment B over Treatment A for Cmax of Dextromethorphan90% CI: [0.778, 1.144]Linear mixed effects model
Primary
Maximum Observed Plasma Concentration (Cmax) of Dextrorphan
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
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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Treatment A | Maximum Observed Plasma Concentration (Cmax) of Dextrorphan | 433 Nanogram per milliliter (ng/mL) |
| Treatment B | Maximum Observed Plasma Concentration (Cmax) of Dextrorphan | 401 Nanogram per milliliter (ng/mL) |
Comparison: Comparison of Treatment B over Treatment A for Cmax of Dextrorphan90% CI: [0.883, 1.007]Linear mixed effects model
Primary
Maximum Observed Plasma Concentration (Cmax) of Digoxin
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
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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Treatment A | Maximum Observed Plasma Concentration (Cmax) of Digoxin | 1.94 Nanogram per milliliter (ng/mL) |
| Treatment B | Maximum Observed Plasma Concentration (Cmax) of Digoxin | 2.35 Nanogram per milliliter (ng/mL) |
Comparison: Comparison of Treatment B over Treatment A for Cmax of Digoxin90% CI: [1.13, 1.378]Linear mixed effects model
Primary
Maximum Observed Plasma Concentration (Cmax) of Maribavir
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
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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Treatment A | Maximum Observed Plasma Concentration (Cmax) of Maribavir | 17.6 Microgram per milliliter (mcg/mL) |
Primary
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)
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
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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A | 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 |
| Treatment A | 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 |
| Treatment A | 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 |
| Treatment A | 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 |
| Treatment A | 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 |
| Treatment A | 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 |
| Treatment B | 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 | 0.025 Ratio of AUC0-infinity |
| Treatment B | 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 | 0.127 Ratio of AUC0-infinity |
| Treatment B | 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 | 0.056 Ratio of AUC0-infinity |
| Treatment B | 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 | NA Ratio of AUC0-infinity |
| Treatment B | 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 | 0.008 Ratio of AUC0-infinity |
| Treatment B | 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 | 0.014 Ratio of AUC0-infinity |
Primary
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)
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
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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Treatment A | 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 |
| Treatment B | 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 |
Comparison: Comparison of Treatment B over Treatment A for Dextromethorphan/Dextrorphan (Parent/Metabolite) AUClast ratio90% CI: [0.721, 1.138]Linear mixed effects model
Primary
Pre-dose Concentration (C0) of Maribavir
C0 is the lowest concentration reached by a drug before the next dose is administered.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Treatment A | Pre-dose Concentration (C0) of Maribavir | 2.64 Microgram per milliliter (mcg/mL) |
Primary
Terminal Half-life (t1/2) of Dextromethorphan
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
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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A | Terminal Half-life (t1/2) of Dextromethorphan | Participant 1 | 15.86 Hour (h) |
| Treatment A | Terminal Half-life (t1/2) of Dextromethorphan | Participant 2 | 9.09 Hour (h) |
| Treatment A | Terminal Half-life (t1/2) of Dextromethorphan | Participant 3 | NA Hour (h) |
| Treatment A | Terminal Half-life (t1/2) of Dextromethorphan | Participant 4 | 9.82 Hour (h) |
| Treatment A | Terminal Half-life (t1/2) of Dextromethorphan | Participant 5 | 6.86 Hour (h) |
| Treatment A | Terminal Half-life (t1/2) of Dextromethorphan | Participant 6 | 6.71 Hour (h) |
| Treatment B | Terminal Half-life (t1/2) of Dextromethorphan | Participant 5 | 5.58 Hour (h) |
| Treatment B | Terminal Half-life (t1/2) of Dextromethorphan | Participant 1 | 16.17 Hour (h) |
| Treatment B | Terminal Half-life (t1/2) of Dextromethorphan | Participant 4 | 8.72 Hour (h) |
| Treatment B | Terminal Half-life (t1/2) of Dextromethorphan | Participant 2 | NA Hour (h) |
| Treatment B | Terminal Half-life (t1/2) of Dextromethorphan | Participant 6 | 7.03 Hour (h) |
| Treatment B | Terminal Half-life (t1/2) of Dextromethorphan | Participant 3 | 6.43 Hour (h) |
Primary
Terminal Half-life (t1/2) of Dextrorphan
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
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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Treatment A | Terminal Half-life (t1/2) of Dextrorphan | 4.42 Hour (h) |
| Treatment B | Terminal Half-life (t1/2) of Dextrorphan | 4.16 Hour (h) |
Primary
Terminal Half-life (t1/2) of Digoxin
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
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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Treatment A | Terminal Half-life (t1/2) of Digoxin | 41.5 Hour (h) |
| Treatment B | Terminal Half-life (t1/2) of Digoxin | 41.8 Hour (h) |
Primary
Terminal Half-life (t1/2) of Maribavir
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
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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Treatment A | Terminal Half-life (t1/2) of Maribavir | 4.04 Hour (h) |
Primary
Time to Reach Maximum Plasma Concentration (Tmax) of Dextromethorphan
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
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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment A | Time to Reach Maximum Plasma Concentration (Tmax) of Dextromethorphan | 3.00 Hour (h) |
| Treatment B | Time to Reach Maximum Plasma Concentration (Tmax) of Dextromethorphan | 3.00 Hour (h) |
Primary
Time to Reach Maximum Plasma Concentration (Tmax) of Dextrorphan
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
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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment A | Time to Reach Maximum Plasma Concentration (Tmax) of Dextrorphan | 2.00 Hour (h) |
| Treatment B | Time to Reach Maximum Plasma Concentration (Tmax) of Dextrorphan | 2.00 Hour (h) |
Primary
Time to Reach Maximum Plasma Concentration (Tmax) of Digoxin
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
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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment A | Time to Reach Maximum Plasma Concentration (Tmax) of Digoxin | 1.00 Hour (h) |
| Treatment B | Time to Reach Maximum Plasma Concentration (Tmax) of Digoxin | 1.00 Hour (h) |
Primary
Time to Reach Maximum Plasma Concentration (Tmax) of Maribavir
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
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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment A | Time to Reach Maximum Plasma Concentration (Tmax) of Maribavir | 2.00 Hour (h) |
Primary
Volume of Distribution Divided by the Fraction of Dose Absorbed (Vz/F) of Dextromethorphan
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
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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A | Volume of Distribution Divided by the Fraction of Dose Absorbed (Vz/F) of Dextromethorphan | Participant 1 | 2360.54 Liter (L) |
| Treatment A | Volume of Distribution Divided by the Fraction of Dose Absorbed (Vz/F) of Dextromethorphan | Participant 2 | 14008.68 Liter (L) |
| Treatment A | Volume of Distribution Divided by the Fraction of Dose Absorbed (Vz/F) of Dextromethorphan | Participant 3 | NA Liter (L) |
| Treatment A | Volume of Distribution Divided by the Fraction of Dose Absorbed (Vz/F) of Dextromethorphan | Participant 4 | 2519.11 Liter (L) |
| Treatment A | Volume of Distribution Divided by the Fraction of Dose Absorbed (Vz/F) of Dextromethorphan | Participant 5 | 6142.85 Liter (L) |
| Treatment A | Volume of Distribution Divided by the Fraction of Dose Absorbed (Vz/F) of Dextromethorphan | Participant 6 | 10836.77 Liter (L) |
| Treatment B | Volume of Distribution Divided by the Fraction of Dose Absorbed (Vz/F) of Dextromethorphan | Participant 5 | 5796.87 Liter (L) |
| Treatment B | Volume of Distribution Divided by the Fraction of Dose Absorbed (Vz/F) of Dextromethorphan | Participant 1 | 3904.44 Liter (L) |
| Treatment B | Volume of Distribution Divided by the Fraction of Dose Absorbed (Vz/F) of Dextromethorphan | Participant 4 | 3931.63 Liter (L) |
| Treatment B | Volume of Distribution Divided by the Fraction of Dose Absorbed (Vz/F) of Dextromethorphan | Participant 2 | NA Liter (L) |
| Treatment B | Volume of Distribution Divided by the Fraction of Dose Absorbed (Vz/F) of Dextromethorphan | Participant 6 | 16835.78 Liter (L) |
| Treatment B | Volume of Distribution Divided by the Fraction of Dose Absorbed (Vz/F) of Dextromethorphan | Participant 3 | 11078.42 Liter (L) |
Primary
Volume of Distribution Divided by the Fraction of Dose Absorbed (Vz/F) of Digoxin
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
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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Treatment A | Volume of Distribution Divided by the Fraction of Dose Absorbed (Vz/F) of Digoxin | 946 Liter (L) |
| Treatment B | Volume of Distribution Divided by the Fraction of Dose Absorbed (Vz/F) of Digoxin | 809 Liter (L) |
Secondary
Number of Participants With Clinically Significant Changes Reported as TEAE in Physical Examination, Vital Signs, 12-lead ECGs, Hematology, Blood Chemistry and Urinalysis
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
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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment A | 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 |
| Treatment A | 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 |
| Treatment A | 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 |
| Treatment A | 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 |
| Treatment A | 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 |
| Treatment A | 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 |
| Treatment B | 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 |
| Treatment B | 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 |
| Treatment B | 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 |
| Treatment B | 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 |
| Treatment B | 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 |
| Treatment B | 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 |
Secondary
Number of Participants With Study-related Adverse Events (AEs), Serious Adverse Events (SAEs) and Treatment-emergent Adverse Events (TEAEs)
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)
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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment A | Number of Participants With Study-related Adverse Events (AEs), Serious Adverse Events (SAEs) and Treatment-emergent Adverse Events (TEAEs) | Study related TEAE | 4 Participants |
| Treatment A | Number of Participants With Study-related Adverse Events (AEs), Serious Adverse Events (SAEs) and Treatment-emergent Adverse Events (TEAEs) | Serious AE | 0 Participants |
| Treatment A | Number of Participants With Study-related Adverse Events (AEs), Serious Adverse Events (SAEs) and Treatment-emergent Adverse Events (TEAEs) | Any TEAE | 4 Participants |
| Treatment B | Number of Participants With Study-related Adverse Events (AEs), Serious Adverse Events (SAEs) and Treatment-emergent Adverse Events (TEAEs) | Study related TEAE | 12 Participants |
| Treatment B | Number of Participants With Study-related Adverse Events (AEs), Serious Adverse Events (SAEs) and Treatment-emergent Adverse Events (TEAEs) | Serious AE | 0 Participants |
| Treatment B | Number of Participants With Study-related Adverse Events (AEs), Serious Adverse Events (SAEs) and Treatment-emergent Adverse Events (TEAEs) | Any TEAE | 12 Participants |