Healthy Volunteers
Conditions
Brief summary
The study will have 2 parts, Part 1 and Part 2. Participants will only participate in one part. The main aim of Part 1 of this study is to check the ability of a single dose of maribavir pediatric formulation to be absorbed in the digestive tract compared to commercial tablet formulation and to check how a high-fat, high-calorie meal affects absorption, distribution, and elimination of maribavir pediatric formulation given orally as water suspension. The main aim of Part 2 of this study is to assess the stomach acid reducing effect of multiple doses of rabeprazole on absorption, distribution, and elimination of maribavir pediatric formulation given orally as water suspension. Each participant will stay in the study clinic from the day before the first treatment until the day after the last treatment.
Detailed description
Part 1 is a crossover design with three treatments (Treatments A, B, and C), six sequences, and three periods. The relative bioavailability of 200 milligrams (mg) maribavir pediatric formulation administered orally as water suspension under fasting conditions (Treatment B) will be compared to 200 mg maribavir commercial tablet administered orally under fasting conditions (Treatment A). In addition, the effect of food on the pharmacokinetics (PK) of 200 mg maribavir pediatric formulation administered orally as water suspension under fasting conditions (Treatment B) and fed conditions (Treatment C) will be assessed. In each sequence, participants will receive three treatments (Treatments A, B, and C) per schedule. * Sequence 1: Treatment A + Treatment B + Treatment C * Sequence 2: Treatment A + Treatment C + Treatment B * Sequence 3: Treatment B + Treatment A + Treatment C * Sequence 4: Treatment B + Treatment C + Treatment A * Sequence 5: Treatment C + Treatment A + Treatment B * Sequence 6: Treatment C + Treatment B + Treatment A Part 2 is a single fixed-sequence design with two treatments (Treatments D and E). The two treatments will be administered to evaluate the gastric acid-reducing effect of multiple doses of rabeprazole on the PK of a single dose of 200 mg maribavir pediatric formulation administered orally as water suspension.
Interventions
DRUGMaribavir Commercial Tablet Formulation
Maribavir commercial tablet.
DRUGMaribavir Pediatric Powder-for-oral Suspension Formulation
Maribavir pediatric powder-for-oral suspension.
DRUGRabeprazole
Rabeprazole tablet.
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* An understanding, ability, and willingness to fully comply with study procedures and restrictions and to voluntarily sign (personally or via a legally authorized representative) informed consent form to participate in the study. * Age 18 to 55 years, inclusive at the time of consent, at the screening visit. * Male, or non-pregnant, non-breastfeeding female who agrees to comply with any applicable contraceptive requirements of the protocol or female of non-childbearing potential. * Body mass index (BMI) between 18.0 and 30.0 kilogram per meter square (kg/m\^2), inclusive with a body weight greater than (\>) 50 kilograms (kg) (110 pounds \[lbs\]), at the screening visit. * Healthy as determined by the Investigator or designee on the basis of screening evaluations and medical history. * Hemoglobin for males greater than or equal to (\>=) 135.0 gram per liter (g/L) and females \>=120.0 g/L, at the screening visit and on Day -1 of Treatment Period 1. * Ability to swallow a dose of maribavir or rabeprazole.
Exclusion criteria
* History or presence of gastritis, gastrointestinal (GI) tract disorder, hepatic disorder or cholecystectomy, history of treated or untreated Helicobacter pylori, ulcer disease or other clinical condition which, in the opinion of the investigator or designee, may affect the absorption, distribution, metabolism, or elimination of the study drugs. * History of any hematological, hepatic, respiratory, cardiovascular, renal, neurological or psychiatric disease, gall bladder removal, or current recurrent disease that could affect the action, absorption, or disposition of the study drugs, or clinical or laboratory assessments. * Current or relevant history of physical or psychiatric illness, any medical disorder that may require treatment or make the participant unlikely to fully complete the study, or any condition that presents undue risk from the study drugs or procedures. * Known or suspected intolerance or hypersensitivity to maribavir or rabeprazole (Part 2 only), closely related compounds, or any of the stated ingredients and excipients. * Significant illness, as judged by the Investigator or designee, within 2 weeks of the first dose of the investigational drug (ID). * Has diarrhea within 4 hours of the first dose of the ID. * Donation of blood or blood products (example, plasma or platelets) within 60 days prior to receiving the first dose of the ID. * Within 30 days prior to the first dose of the ID: * Have used any investigational product (if elimination half-life is less than \[\<\] 6 days, otherwise 5 half-lives). * Have been enrolled in a clinical study (including vaccine studies) that, in the Investigator or designee's opinion, may impact this Takeda-sponsored study. * Have had any substantial changes in eating habits, as assessed by the Investigator or designee. * Systolic blood pressure \>140 millimeters of mercury (mmHg) or \<90 mmHg, and/or diastolic blood pressure \>90 mmHg or \<50 mmHg, at the screening visit. * Corrected QT interval (QTc) \>450 millisecond (msec) at the screening visit. If QTc exceeds 450 msec, the ECG should be repeated two more times and the average of the three QTc values should be used to determine the participant's eligibility. * Known history of alcohol or other substance abuse within the last year. * Male participants who consume more than 21 units of alcohol per week or three units per day. Female participants who consume more than 14 units of alcohol per week or two units per day (one alcohol unit = one beer or one wine \[5 ounces \[oz\]/150 milliliter \[mL\]\] or one liquor \[1.5 oz/40 mL\] or 0.75 oz alcohol). * A positive screen for alcohol or drugs of abuse at the screening visit or on Day -1 of Treatment Period 1. Urine samples are to be tested for amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, opiates, and phencyclidine. * A positive Human immunodeficiency virus (HIV), Hepatitis B surface antigen (HBsAg), or Hepatitis C virus (HCV) antibody screen at the screening visit. * Use of tobacco in any form (example, smoking or chewing) or other nicotine-containing products in any form (example, gum, patch). Ex-users must self-report that they have stopped using tobacco for at least 3 months prior to receiving the first dose. * Routine consumption of more than two units of caffeine per day or participants 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, three 1-oz \[85 grams \[g\]\] chocolate bars). Decaffeinated coffee, tea, or cola are not considered to contain caffeine. * Current use of any prescription medication with the exception of hormonal contraceptives and hormonal replacement therapy. Current use of any over-the-counter (OTC) medication (including OTC multi-vitamin, herbal, or homeopathic preparations) within 14 days of the first dose. Hormonal contraceptives and hormonal replacement therapy may be permitted if the female participant has been on the same stable dose for at least 3 months prior to first dose. * Current use of antacids, proton pump inhibitors (PPIs), or histamine type 2 (H2) antagonists within 14 days of the first dose, except for on-study rabeprazole. * Inability or unwillingness to consume 100 percent of the high-fat, high-calorie meal (including participants with lactose or gluten intolerance). * Female participants with a positive pregnancy test at the screening visit or on Day -1 of Treatment Period 1 or who are lactating. * Participants on a diet incompatible with the on-study diet, in the opinion of the Investigator or designee, within the 30 days prior to the first dosing and throughout the study. * Recent history (within 1 month) of oral/nasal cavity infections, history of gastroesophageal reflux, asthma treatment with albuterol, or zinc supplementation. * Participants with dry mouth syndrome or burning mouth syndrome or participants suffering from dysgeusia.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Parts 1 and 2: Maximum Observed Plasma Concentration (Cmax) of Maribavir | Part 1 Day 1 and Part 2 Treatment D Day 1 and Treatment E Day 5: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours post-dose | Cmax was defined as maximum observed concentration of maribavir in plasma. |
| Parts 1 and 2: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Maribavir | Part 1 Day 1 and Part 2 Treatment D Day 1 and Treatment E Day 5: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours post-dose | AUClast was defined as the area under the concentration-time curve from time 0 to the time of the last quantifiable concentration of maribavir in plasma. |
| Parts 1 and 2: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-infinity) of Maribavir | Part 1 Day 1 and Part 2 Treatment D Day 1 and Treatment E Day 5: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours post-dose | AUC0-infinity was defined as the area under the plasma concentration-time curve from time 0 to infinity of maribavir in plasma. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Parts 1 and 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Parts 1 and 2: From start of study drug administration up to follow-up (Day 16) | A TEAE was defined as an adverse event (AE) that was starting or worsening at the time of or after the first dose of maribavir administered in the study. An serious adverse event (SAE) was defined as any untoward medical occurrence that at any dose resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect; was an important medical event that satisfies any of the following: might require intervention to prevent items 1 through 5 above and might exposed the participant to danger, even though the event is not immediately life threatening or fatal or does not result in hospitalization. Any clinically significant changes in vital signs, electrocardiogram (ECG) values and clinical laboratory parameters were considered as TEAEs. |
| Number of Participants Based on Severity of TEAEs | Parts 1 and 2: From start of study drug administration up to follow-up (Day 16) | Severity of TEAEs were determined by following criteria: Mild: An AE that was usually transient and might require only minimal treatment or therapeutic intervention. The event did not generally interfere with usual activities of daily living; Moderate: An AE that was usually alleviated with additional specific therapeutic intervention. The event interfered with usual activities of daily living, causing discomfort but possessed no significant or permanent risk of harm to the research participant; Severe: An AE that interrupted usual activities of daily living, or significantly affects clinical status, or might require intensive therapeutic intervention. |
| Number of Participants Based on Causality of TEAEs | Parts 1 and 2: From start of study drug administration up to follow-up (Day 16) | The causality relationship of each AE to the study drug was assessed using the following categories: Related: An AE that followed a reasonable temporal sequence from administration of a drug (including the course after withdrawal of the drug), or for which a causal relationship was at least a reasonable possibility, that was, the relationship could not be ruled out, although factors other than the drug, such as underlying diseases, complications, concomitant drugs and concurrent treatments, might also be responsible; Not Related: An AE that did not follow a reasonable temporal sequence from administration of a drug and/or that could reasonably be explained by other factors, such as underlying diseases, complications, concomitant medications and concurrent treatments. Number of participants based on causality of TEAEs as assessed by the Investigator were reported. |
Countries
United States
Participant flow
Recruitment details
This study was conducted at single center in the United States from 25 July 2023 to 01 September 2023.
Pre-assignment details
A total of 32 participants were enrolled and randomized in this 2-part (18 in Part 1 and 14 in Part 2) study. Part 1 consisted of 3 treatment-periods and participants were randomized into one of 6 treatment sequences: ABC, ACB, BAC, BCA, CAB, or CBA. Part 2 consisted of 2-treatment periods and was a single fixed-sequence design with 2 treatments: Treatment D and E.
Participants by arm
| Arm | Count |
|---|---|
| Part 1, Sequence 1: Treatment A + Treatment B + Treatment C On Day 1 of Treatment Period 1, participants received maribavir single 200 milligrams (mg) commercial tablet, under fasting conditions (Treatment A). On Day 1 of Treatment Period 2, participants received single oral dose of maribavir 200 mg pediatric powder-for-oral suspension under fasting conditions (Treatment B). On Day 1 of Treatment Period 3, participants received single oral dose of maribavir 200 mg pediatric powder-for-oral suspension administered with a high fat/high calorie meal (Treatment C). There was a washout period of a minimum of 3 days between each Treatment Period. | 3 |
| Part 1, Sequence 2: Treatment A + Treatment C + Treatment B On Day 1 of Treatment Period 1, participants received maribavir single 200 mg commercial tablet under fasting conditions (Treatment A), followed by single oral dose of maribavir 200 mg pediatric powder-for-oral suspension on Day 1 of Treatment Period 2 administered with a high fat/high calorie meal (Treatment C), and further followed by single oral dose of maribavir 200 mg pediatric powder-for-oral suspension on Day 1 of Treatment Period 3 under fasting conditions (Treatment B). There was a washout period of a minimum of 3 days between each Treatment Period. | 3 |
| Part 1, Sequence 3: Treatment B + Treatment A + Treatment C On Day 1 of Treatment Period 1, participants received a single oral dose of maribavir 200 mg pediatric powder-for-oral suspension under fasting conditions (Treatment B). On Day 1 of Treatment Period 2, participants received maribavir single 200 mg commercial tablet under fasting conditions (Treatment A). On Day 1 of Treatment Period 3, participants received single oral dose of maribavir 200 mg pediatric powder-for-oral suspension administered with a high fat/high calorie meal (Treatment C). There was a washout period of a minimum of 3 days between each Treatment Period. | 3 |
| Part 1, Sequence 4: Treatment B + Treatment C + Treatment A On Day 1 of Treatment Period 1, participants received single oral dose of maribavir 200 mg pediatric powder-for-oral suspension under fasting conditions (Treatment B). On Day 1 of Treatment Period 2 participants received single oral dose of maribavir 200 mg pediatric powder-for-oral suspension administered with a high fat/high calorie meal (Treatment C). On Day 1 of Treatment Period 3, participants received maribavir single 200 mg commercial tablet under fasting conditions (Treatment A). There was a washout period of a minimum of 3 days between each Treatment Period. | 3 |
| Part 1, Sequence 5: Treatment C + Treatment A + Treatment B On Day 1 of Treatment Period 1, participants received maribavir 200 mg pediatric powder-for-oral suspension, single oral dose administered with a high fat/high calorie meal (Treatment C). On Day 1 of Treatment Period 2, participants received maribavir single 200 mg commercial tablet under fasting conditions (Treatment A). On Day 1 of Treatment Period 3, participants received single oral dose of maribavir 200 mg pediatric powder-for-oral suspension under fasting conditions (Treatment B). There was a washout period of a minimum of 3 days between each Treatment Period. | 3 |
| Part 1, Sequence 6: Treatment C + Treatment B+ Treatment A On Day 1 of Treatment Period 1, participants received maribavir 200 mg pediatric powder-for-oral suspension, single oral dose administered with a high fat/high calorie meal (Treatment C). On Day 1 of Treatment Period 2, participants received single oral dose of maribavir 200 mg pediatric powder-for-oral suspension under fasting conditions (Treatment B). On Day 1 of Treatment Period 3, participants received maribavir single 200 mg commercial tablet under fasting conditions (Treatment A). There was a washout period of a minimum of 3 days between each Treatment Period. | 3 |
| Part 2: Treatment D + E: Maribavir 200 mg + Rabeprazole 20 mg On Day 1 of Treatment Period 1, participants received a single oral dose of 200 mg maribavir powder-for-oral suspension formulation under fasting conditions (Treatment D). On Days 1 to 5 of Treatment Period 2, participants received oral doses of 20 mg rabeprazole, once daily, under fasting conditions. On the morning of Day 5 of Treatment Period 2, two hours after rabeprazole dosing, participants received a single oral dose of 200 mg maribavir powder-for-oral suspension formulation under fasting conditions (Treatment E). There was a washout period of a minimum of 3 days between maribavir dosing in Treatment Period 1 and first dose of rabeprazole in Treatment Period 2. | 14 |
| Total | 32 |
Baseline characteristics
| Characteristic | Part 1, Sequence 1: Treatment A + Treatment B + Treatment C | Part 1, Sequence 2: Treatment A + Treatment C + Treatment B | Part 1, Sequence 3: Treatment B + Treatment A + Treatment C | Part 1, Sequence 4: Treatment B + Treatment C + Treatment A | Part 1, Sequence 5: Treatment C + Treatment A + Treatment B | Part 1, Sequence 6: Treatment C + Treatment B+ Treatment A | Part 2: Treatment D + E: Maribavir 200 mg + Rabeprazole 20 mg | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 14 Participants | 32 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 1 Participants | 2 Participants | 1 Participants | 3 Participants | 2 Participants | 9 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 2 Participants | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 5 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 4 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 1 Participants | 1 Participants | 3 Participants | 3 Participants | 3 Participants | 10 Participants | 23 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants | 2 Participants | 2 Participants | 1 Participants | 6 Participants | 15 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 8 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 18 | 0 / 18 | 0 / 14 | 0 / 14 | 0 / 14 |
| other Total, other adverse events | 2 / 18 | 0 / 18 | 2 / 18 | 0 / 14 | 2 / 14 | 1 / 14 |
| serious Total, serious adverse events | 0 / 18 | 0 / 18 | 0 / 18 | 0 / 14 | 0 / 14 | 0 / 14 |
Outcome results
Primary
Parts 1 and 2: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-infinity) of Maribavir
AUC0-infinity was defined as the area under the plasma concentration-time curve from time 0 to infinity of maribavir in plasma.
Time frame: Part 1 Day 1 and Part 2 Treatment D Day 1 and Treatment E Day 5: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours post-dose
Population: PK set included all participants who received at least one dose of maribavir, did not vomit or had diarrhea within four hours of the maribavir dosing, and had five or more post-dose time points with evaluable post-dose maribavir concentration values that enabled NCA. Here, Overall Number of Participants Analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1, Treatment A: Maribavir 200 mg | Parts 1 and 2: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-infinity) of Maribavir | 59.1 mcg*h/mL | Geometric Coefficient of Variation 55.9 |
| Part 1, Treatment B: Maribavir 200 mg | Parts 1 and 2: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-infinity) of Maribavir | 59.1 mcg*h/mL | Geometric Coefficient of Variation 56.3 |
| Part 1, Treatment C: Maribavir 200 mg | Parts 1 and 2: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-infinity) of Maribavir | 48.2 mcg*h/mL | Geometric Coefficient of Variation 57.6 |
| Part 2, Treatment D: Maribavir 200 mg | Parts 1 and 2: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-infinity) of Maribavir | 57.2 mcg*h/mL | Geometric Coefficient of Variation 38.5 |
| Part 2, Treatment E: Rabeprazole 20 mg + Maribavir 200 mg | Parts 1 and 2: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-infinity) of Maribavir | 50.1 mcg*h/mL | Geometric Coefficient of Variation 35.4 |
Comparison: Comparison of AUC0-infinity of Maribavir: Part 1: Treatment B (Test) versus Treatment A (Reference)90% CI: [94.12, 106.11]
Comparison: Comparison of AUC0-infinity of Maribavir: Part 1: Treatment C (Test) versus Treatment B (Reference)90% CI: [76.93, 86.73]
Comparison: Comparison of AUC0-infinity of Maribavir: Part 2: Treatment E (Test) versus Treatment D (Reference)90% CI: [76.94, 102.78]
Primary
Parts 1 and 2: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Maribavir
AUClast was defined as the area under the concentration-time curve from time 0 to the time of the last quantifiable concentration of maribavir in plasma.
Time frame: Part 1 Day 1 and Part 2 Treatment D Day 1 and Treatment E Day 5: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours post-dose
Population: PK set included all participants who received at least one dose of maribavir, did not vomit or had diarrhea within four hours of the maribavir dosing, and had five or more post-dose time points with evaluable post-dose maribavir concentration values that enabled NCA.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1, Treatment A: Maribavir 200 mg | Parts 1 and 2: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Maribavir | 55.5 microgram*hour per milliliter (mcg*h/mL) | Geometric Coefficient of Variation 52.6 |
| Part 1, Treatment B: Maribavir 200 mg | Parts 1 and 2: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Maribavir | 54.2 microgram*hour per milliliter (mcg*h/mL) | Geometric Coefficient of Variation 50.2 |
| Part 1, Treatment C: Maribavir 200 mg | Parts 1 and 2: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Maribavir | 44.4 microgram*hour per milliliter (mcg*h/mL) | Geometric Coefficient of Variation 51.9 |
| Part 2, Treatment D: Maribavir 200 mg | Parts 1 and 2: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Maribavir | 53.9 microgram*hour per milliliter (mcg*h/mL) | Geometric Coefficient of Variation 37.3 |
| Part 2, Treatment E: Rabeprazole 20 mg + Maribavir 200 mg | Parts 1 and 2: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Maribavir | 37.7 microgram*hour per milliliter (mcg*h/mL) | Geometric Coefficient of Variation 36.8 |
Comparison: Comparison of AUClast of Maribavir: Part 1: Treatment B (Test) versus Treatment A (Reference)90% CI: [91.39, 104.2]
Comparison: Comparison of AUClast of Maribavir: Part 1: Treatment C (Test) versus Treatment B (Reference)90% CI: [76.84, 87.61]
Comparison: Comparison of AUClast of Maribavir: Part 2: Treatment E (Test) versus Treatment D (Reference)90% CI: [60.11, 81.51]
Primary
Parts 1 and 2: Maximum Observed Plasma Concentration (Cmax) of Maribavir
Cmax was defined as maximum observed concentration of maribavir in plasma.
Time frame: Part 1 Day 1 and Part 2 Treatment D Day 1 and Treatment E Day 5: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours post-dose
Population: Pharmacokinetic (PK) set included all participants who received at least one dose of maribavir, did not vomit or had diarrhea within four hours of the maribavir dosing, and had five or more post-dose time points with evaluable post-dose maribavir concentration values that enabled non-compartmental analysis (NCA).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1, Treatment A: Maribavir 200 mg | Parts 1 and 2: Maximum Observed Plasma Concentration (Cmax) of Maribavir | 12.6 microgram per milliliter (mcg/mL) | Geometric Coefficient of Variation 26.3 |
| Part 1, Treatment B: Maribavir 200 mg | Parts 1 and 2: Maximum Observed Plasma Concentration (Cmax) of Maribavir | 10.4 microgram per milliliter (mcg/mL) | Geometric Coefficient of Variation 26.2 |
| Part 1, Treatment C: Maribavir 200 mg | Parts 1 and 2: Maximum Observed Plasma Concentration (Cmax) of Maribavir | 5.98 microgram per milliliter (mcg/mL) | Geometric Coefficient of Variation 28.3 |
| Part 2, Treatment D: Maribavir 200 mg | Parts 1 and 2: Maximum Observed Plasma Concentration (Cmax) of Maribavir | 10.2 microgram per milliliter (mcg/mL) | Geometric Coefficient of Variation 19.9 |
| Part 2, Treatment E: Rabeprazole 20 mg + Maribavir 200 mg | Parts 1 and 2: Maximum Observed Plasma Concentration (Cmax) of Maribavir | 4.98 microgram per milliliter (mcg/mL) | Geometric Coefficient of Variation 49.9 |
Comparison: Comparison of Cmax of Maribavir: Part 1: Treatment B (Test) versus Treatment A (Reference)90% CI: [74.31, 90.91]
Comparison: Comparison of Cmax of Maribavir: Part 1: Treatment C (Test) versus Treatment B (Reference)90% CI: [52.18, 63.84]
Comparison: Comparison of Cmax of Maribavir: Part 2: Treatment E (Test) versus Treatment D (Reference)90% CI: [40.07, 60]
Secondary
Number of Participants Based on Causality of TEAEs
The causality relationship of each AE to the study drug was assessed using the following categories: Related: An AE that followed a reasonable temporal sequence from administration of a drug (including the course after withdrawal of the drug), or for which a causal relationship was at least a reasonable possibility, that was, the relationship could not be ruled out, although factors other than the drug, such as underlying diseases, complications, concomitant drugs and concurrent treatments, might also be responsible; Not Related: An AE that did not follow a reasonable temporal sequence from administration of a drug and/or that could reasonably be explained by other factors, such as underlying diseases, complications, concomitant medications and concurrent treatments. Number of participants based on causality of TEAEs as assessed by the Investigator were reported.
Time frame: Parts 1 and 2: From start of study drug administration up to follow-up (Day 16)
Population: Safety set included all participants who received at least one dose of maribavir.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1, Treatment A: Maribavir 200 mg | Number of Participants Based on Causality of TEAEs | Related TEAEs | 1 Participants |
| Part 1, Treatment A: Maribavir 200 mg | Number of Participants Based on Causality of TEAEs | Not Related TEAEs | 1 Participants |
| Part 1, Treatment B: Maribavir 200 mg | Number of Participants Based on Causality of TEAEs | Related TEAEs | 0 Participants |
| Part 1, Treatment B: Maribavir 200 mg | Number of Participants Based on Causality of TEAEs | Not Related TEAEs | 0 Participants |
| Part 1, Treatment C: Maribavir 200 mg | Number of Participants Based on Causality of TEAEs | Related TEAEs | 1 Participants |
| Part 1, Treatment C: Maribavir 200 mg | Number of Participants Based on Causality of TEAEs | Not Related TEAEs | 1 Participants |
| Part 2, Treatment D: Maribavir 200 mg | Number of Participants Based on Causality of TEAEs | Related TEAEs | 0 Participants |
| Part 2, Treatment D: Maribavir 200 mg | Number of Participants Based on Causality of TEAEs | Not Related TEAEs | 0 Participants |
| Part 2, Treatment E: Rabeprazole 20 mg + Maribavir 200 mg | Number of Participants Based on Causality of TEAEs | Related TEAEs | 0 Participants |
| Part 2, Treatment E: Rabeprazole 20 mg + Maribavir 200 mg | Number of Participants Based on Causality of TEAEs | Not Related TEAEs | 2 Participants |
| Part 2, Treatment E2: Maribavir 200 mg | Number of Participants Based on Causality of TEAEs | Related TEAEs | 0 Participants |
| Part 2, Treatment E2: Maribavir 200 mg | Number of Participants Based on Causality of TEAEs | Not Related TEAEs | 1 Participants |
Secondary
Number of Participants Based on Severity of TEAEs
Severity of TEAEs were determined by following criteria: Mild: An AE that was usually transient and might require only minimal treatment or therapeutic intervention. The event did not generally interfere with usual activities of daily living; Moderate: An AE that was usually alleviated with additional specific therapeutic intervention. The event interfered with usual activities of daily living, causing discomfort but possessed no significant or permanent risk of harm to the research participant; Severe: An AE that interrupted usual activities of daily living, or significantly affects clinical status, or might require intensive therapeutic intervention.
Time frame: Parts 1 and 2: From start of study drug administration up to follow-up (Day 16)
Population: Safety set included all participants who received at least one dose of maribavir.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1, Treatment A: Maribavir 200 mg | Number of Participants Based on Severity of TEAEs | Moderate | 0 Participants |
| Part 1, Treatment A: Maribavir 200 mg | Number of Participants Based on Severity of TEAEs | Mild | 2 Participants |
| Part 1, Treatment A: Maribavir 200 mg | Number of Participants Based on Severity of TEAEs | Severe | 0 Participants |
| Part 1, Treatment B: Maribavir 200 mg | Number of Participants Based on Severity of TEAEs | Moderate | 0 Participants |
| Part 1, Treatment B: Maribavir 200 mg | Number of Participants Based on Severity of TEAEs | Mild | 0 Participants |
| Part 1, Treatment B: Maribavir 200 mg | Number of Participants Based on Severity of TEAEs | Severe | 0 Participants |
| Part 1, Treatment C: Maribavir 200 mg | Number of Participants Based on Severity of TEAEs | Moderate | 1 Participants |
| Part 1, Treatment C: Maribavir 200 mg | Number of Participants Based on Severity of TEAEs | Mild | 1 Participants |
| Part 1, Treatment C: Maribavir 200 mg | Number of Participants Based on Severity of TEAEs | Severe | 0 Participants |
| Part 2, Treatment D: Maribavir 200 mg | Number of Participants Based on Severity of TEAEs | Moderate | 0 Participants |
| Part 2, Treatment D: Maribavir 200 mg | Number of Participants Based on Severity of TEAEs | Mild | 0 Participants |
| Part 2, Treatment D: Maribavir 200 mg | Number of Participants Based on Severity of TEAEs | Severe | 0 Participants |
| Part 2, Treatment E: Rabeprazole 20 mg + Maribavir 200 mg | Number of Participants Based on Severity of TEAEs | Moderate | 1 Participants |
| Part 2, Treatment E: Rabeprazole 20 mg + Maribavir 200 mg | Number of Participants Based on Severity of TEAEs | Mild | 1 Participants |
| Part 2, Treatment E: Rabeprazole 20 mg + Maribavir 200 mg | Number of Participants Based on Severity of TEAEs | Severe | 0 Participants |
| Part 2, Treatment E2: Maribavir 200 mg | Number of Participants Based on Severity of TEAEs | Mild | 1 Participants |
| Part 2, Treatment E2: Maribavir 200 mg | Number of Participants Based on Severity of TEAEs | Severe | 0 Participants |
| Part 2, Treatment E2: Maribavir 200 mg | Number of Participants Based on Severity of TEAEs | Moderate | 0 Participants |
Secondary
Parts 1 and 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
A TEAE was defined as an adverse event (AE) that was starting or worsening at the time of or after the first dose of maribavir administered in the study. An serious adverse event (SAE) was defined as any untoward medical occurrence that at any dose resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect; was an important medical event that satisfies any of the following: might require intervention to prevent items 1 through 5 above and might exposed the participant to danger, even though the event is not immediately life threatening or fatal or does not result in hospitalization. Any clinically significant changes in vital signs, electrocardiogram (ECG) values and clinical laboratory parameters were considered as TEAEs.
Time frame: Parts 1 and 2: From start of study drug administration up to follow-up (Day 16)
Population: Safety set included all participants who received at least one dose of maribavir.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1, Treatment A: Maribavir 200 mg | Parts 1 and 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | TEAEs | 2 Participants |
| Part 1, Treatment A: Maribavir 200 mg | Parts 1 and 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 0 Participants |
| Part 1, Treatment B: Maribavir 200 mg | Parts 1 and 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | TEAEs | 0 Participants |
| Part 1, Treatment B: Maribavir 200 mg | Parts 1 and 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 0 Participants |
| Part 1, Treatment C: Maribavir 200 mg | Parts 1 and 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | TEAEs | 2 Participants |
| Part 1, Treatment C: Maribavir 200 mg | Parts 1 and 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 0 Participants |
| Part 2, Treatment D: Maribavir 200 mg | Parts 1 and 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | TEAEs | 0 Participants |
| Part 2, Treatment D: Maribavir 200 mg | Parts 1 and 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 0 Participants |
| Part 2, Treatment E: Rabeprazole 20 mg + Maribavir 200 mg | Parts 1 and 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | TEAEs | 2 Participants |
| Part 2, Treatment E: Rabeprazole 20 mg + Maribavir 200 mg | Parts 1 and 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 0 Participants |
| Part 2, Treatment E2: Maribavir 200 mg | Parts 1 and 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | TEAEs | 1 Participants |
| Part 2, Treatment E2: Maribavir 200 mg | Parts 1 and 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 0 Participants |