Healthy Volunteers
Conditions
Brief summary
The Purpose of this study is to assess the relative bioavailability, dose proportionality, the impact of food on the rate and extent of absorption, palatability of the selected pediatric formulation of maribavir and the safety and tolerability of two candidate pediatric formulations and the adult tablet formulation of maribavir in healthy participants.
Detailed description
The study will be conducted in two parts (Part 1 and Part 2). Part 1 consists of three treatment periods in six sequences and part 2 consists of four treatment periods in four sequences. In Part 1 two pediatric candidate powder formulations will be compared with maribavir 200mg tablet under fasted conditions in regards to their bioavailability and palatability. In Part 2 dose proportionality and impact of food (a high-fat meal) on the rate and extent of absorption of the selected pediatric formulation will be assessed. The pediatric formulation which will be evaluated in Part 2 will be chosen based on the results of planned analysis of Part 1 PK and palatability data from two candidate pediatric formulations and the doses to be evaluated in Part 2 may be adjusted based on relative bioavailability of the selected pediatric formulation (powder for oral suspension) to the Phase 3 tablet formulation observed in Part 1.
Interventions
DRUGMaribavir
Participants in both part 1 and part 2 of the study will receive maribavir tablet or suspension orally depending upon the treatment sequence allocation for a total of 7 and 10 days respectively.
Sponsors
Shire
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
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 voluntarily provide written, signed, and dated (personally or via a legally-authorized representative) informed consent/and assent as applicable to participate in the study. * Age 18-50 years, inclusive at the time of consent. * Male, or non-pregnant, non-breastfeeding female who agrees to comply with any applicable contraceptive requirements of the protocol or females of non-childbearing potential. * Healthy as determined by the investigator on the basis of screening evaluations. * Hemoglobin for males greater than or equal to (\> or =)135.0 gram per liter (g/L) and females \> or = 120.0 g/L at screening and on Day -1. * Body mass index (BMI) between 18.0 and 30.0 kilogram per meter square (kg/m2) inclusive with a body weight greater than (\>) 50 kg (110 lbs).
Exclusion criteria
* History of any hematological, hepatic, respiratory, cardiovascular, renal, neurological or psychiatric disease, gallbladder removal, or current recurrent disease. * 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 investigational product or procedures. * 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. * Donation of blood or blood products (e.g., 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:a) Have used an investigational product, b) Have been enrolled in a clinical study (including vaccine studies) that, in the investigator's opinion, may impact this study, c) Have had any substantial changes in eating habits, as assessed by the investigator. * Confirmed systolic blood pressure \>139 millimetre of mercury (mmHg) or \< 89 mmHg, and diastolic blood pressure \> 89 mmHg or \< 49 mmHg. * Twelve-lead ECG demonstrating QTc \> 450 millisecond (msec). * 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 3 units per day. Female participants who consume more than 14 units of alcohol per week or 2 units per day. * A positive screen for alcohol or drugs of abuse at screening or on Day -1 of Treatment Period. * A positive human immunodeficiency virus (HIV), HBsAg, or Hepatitis C virus (HCV) antibody screen. * Use of tobacco in any form (e.g., smoking or chewing) or other nicotine-containing products in any form (e.g., gum, patch). * Routine consumption of more than 2 units of caffeine per day or participants who experience caffeine withdrawal headaches. * Prior screen failure, randomization, enrollment, participation in this study or participation in Part 1 of this study. * Current use of any prescription medication with the exception of hormonal replacement therapy. (Current use is defined as use within 30 days of the first dose of investigational product.) Current use of any over the counter medication (including herbal, or homeopathic preparations) within 14 days of the first dose of investigational product. * Current use of antacids and H2 antagonists. * Ingestion of known CYP3A modulators within 7 days of Day 1, Period 1. * Inability or unwillingness to consume 100 percent of high-fat meal in Part 2 (including participants with lactose or gluten intolerance). * History of oral/nasal cavity infections, gastroesophageal reflux, asthma treatment with albuterol, zinc supplementation. * Participants with dry mouth syndrome or burning mouth syndrome or menopausal women suffering from dysgeusia.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | Up to Day 7 | The palatability was evaluated to identify, characterize and quantify the sensory attributes of products, e.g., basic tastes, texture and mouth feel and to assess the overall acceptability. Number of participants responded to palatability assessment up to Day 7 were reported. |
| Area Under the Curve Extrapolated to Infinity, Calculated Using the Observed Value of the Last Non-Zero Concentration (AUC0-Inf) of Maribavir in Plasma | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 20, 24 hours post-dose on Days 1, 4, and 7 | AUC0-Inf of maribavir in plasma was reported. Geometric mean and geometric coefficient of variation percent (CV%) were reported. |
| Part 1: Terminal Half-Life (t1/2) of Maribavir in Plasma | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 20, 24 hours post-dose on Days 1, 4 and 7 | t1/2 of maribavir in plasma was reported. |
| Part 1: Apparent Total Body Clearance Following Extravascular Administration (CL/F) of Maribavir in Plasma | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 20, 24 hours post-dose on Days 1, 4 and 7 | CL/F of maribavir in Plasma was reported. |
| Part 1: Delay Between the Time of Dosing and Time of Appearance of Plasma Concentration (Tlag) of Maribavir in Plasma | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 20, 24 hours post-dose on Day 1, 4 and 7 | Tlag of maribavir in plasma was reported. |
| Part 1: Maximum Concentration (Cmax) Occurred at Time of Maximum Observed Concentration Sampled During a Dosing Interval (Tmax) of Maribavir in Plasma | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 20, 24 hours post-dose on Days 1, 4, and 7 | Cmax defined as maximum concentration occurred at tmax of maribavir in plasma was reported. Geometric mean and geometric coefficient of variation percent (CV%) were reported. |
| Part 1: Time of Maximum Observed Concentration Sampled During a Dosing Interval (Tmax) of Maribavir in Plasma | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 20, 24 hours post-dose on Days 1, 4, and 7 | tmax defined as time of maximum observed concentration sampled during a dosing interval of maribavir in plasma were reported. |
| Part 1: Area Under the Curve From the Time of Dosing to the Last Measurable Concentration (AUC0-last) of Maribavir in Plasma | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 20, 24 hours post-dose on Days 1, 4, and 7 | AUC0-last of maribavir in plasma was reported. Geometric mean and geometric coefficient of variation percent (CV%) were reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinically Significant Changes in Vital Signs Reported as TEAEs | From start of study drug administration up to follow-up (Day 17) | Vital sign assessments included systolic and diastolic blood pressure, pulse rate and body temperature. Any change in vital signs which were deemed clinically significant by the investigator were recorded as TEAE. |
| Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Reported as TEAEs | From start of study drug administration up to follow-up (Day 17) | 12-lead ECG were evaluated. Any change in ECG assessments which are deemed clinically significant by the investigator were reported as TEAE. |
| Number of Participants With Clinically Significant Changes in Clinical Laboratory Results Reported as TEAEs | From start of study drug administration up to follow-up (Day 17) | Clinical laboratory tests included biochemistry, hematology and urinalysis. Any change in clinical laboratory results which are deemed clinically significant by the investigator were reported as TEAE. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | From start of study drug administration up to follow-up (Day 17) | An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily had a causal relationship with this treatment. A TEAE was an adverse event with a start date on or after the first dose of Investigational product (IP), or a start date before the date of the first dose of IP but increased in severity on or after the date of the first dose of IP. Number of participants with TEAEs were reported. |
Countries
United States
Participant flow
Recruitment details
This study was conducted at single site in United States of America from 25 October 2019 (first participant first visit) and 06 January 2020 (last participant last visit).
Pre-assignment details
This study was planned to be conducted in 2 parts: Part 1 and Part 2. However, study was terminated based on planned interim analysis of the data of Part 1, palatability of both pediatric formulations was not acceptable and therefore, Part 2 was not conducted. Participants were randomized to 1 of 6 sequences with treatment A, B and C. Baseline characteristics of participants were only analyzed and reported for overall study period, as planned, and not per treatment to avoid double-counting.
Participants by arm
| Arm | Count |
|---|---|
| Maribavir Participants received 200 milligrams (mg) of maribavir tablet orally (Treatment A) or 200 mg maribavir powder for oral suspension with 32.5 percent (%) drug loading (Treatment B) or maribavir 200 mg powder for oral suspension with 36.1% drug loading (Treatment C) on Day 1 or Day 4 or Day 7 in different sequences of ABC, BCA, CAB, CBA, ACB, and BAC. | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Maribavir |
|---|---|
| Age, Continuous | 33.7 Years STANDARD_DEVIATION 8.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 17 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 16 Participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 20 |
| other Total, other adverse events | 3 / 20 |
| serious Total, serious adverse events | 0 / 20 |
Outcome results
Primary
Area Under the Curve Extrapolated to Infinity, Calculated Using the Observed Value of the Last Non-Zero Concentration (AUC0-Inf) of Maribavir in Plasma
AUC0-Inf of maribavir in plasma was reported. Geometric mean and geometric coefficient of variation percent (CV%) were reported.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 20, 24 hours post-dose on Days 1, 4, and 7
Population: PK set 1 consisted of participants who received at least 1 dose of maribavir, did not vomit within 4 hours post dosing, and had at least 1 evaluable post-dose maribavir concentration value in Part 1. Data for the PK parameters were planned and analyzed based on unique treatment sequence A, B, C. Hence, data was reported separately.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Area Under the Curve Extrapolated to Infinity, Calculated Using the Observed Value of the Last Non-Zero Concentration (AUC0-Inf) of Maribavir in Plasma | 52.5 h*μg/mL | Geometric Coefficient of Variation 49.72 |
| Treatment B | Area Under the Curve Extrapolated to Infinity, Calculated Using the Observed Value of the Last Non-Zero Concentration (AUC0-Inf) of Maribavir in Plasma | 44.5 h*μg/mL | Geometric Coefficient of Variation 56.26 |
| Treatment C | Area Under the Curve Extrapolated to Infinity, Calculated Using the Observed Value of the Last Non-Zero Concentration (AUC0-Inf) of Maribavir in Plasma | 42.4 h*μg/mL | Geometric Coefficient of Variation 60.69 |
90% CI: [76.12, 91.64]ANOVA
90% CI: [73.26, 88.16]ANOVA
Primary
Part 1: Apparent Total Body Clearance Following Extravascular Administration (CL/F) of Maribavir in Plasma
CL/F of maribavir in Plasma was reported.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 20, 24 hours post-dose on Days 1, 4 and 7
Population: PK set 1 consisted of participants who received at least 1 dose of maribavir, did not vomit within 4 hours post dosing, and had at least 1 evaluable post-dose maribavir concentration value in Part 1. Data for the PK parameters were planned and analyzed based on unique treatment sequence A, B, C. Hence, data was reported separately.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Part 1: Apparent Total Body Clearance Following Extravascular Administration (CL/F) of Maribavir in Plasma | 4.21 Liters per hour (L/h) | Standard Deviation 1.99 |
| Treatment B | Part 1: Apparent Total Body Clearance Following Extravascular Administration (CL/F) of Maribavir in Plasma | 5.13 Liters per hour (L/h) | Standard Deviation 2.82 |
| Treatment C | Part 1: Apparent Total Body Clearance Following Extravascular Administration (CL/F) of Maribavir in Plasma | 5.49 Liters per hour (L/h) | Standard Deviation 3.29 |
Primary
Part 1: Area Under the Curve From the Time of Dosing to the Last Measurable Concentration (AUC0-last) of Maribavir in Plasma
AUC0-last of maribavir in plasma was reported. Geometric mean and geometric coefficient of variation percent (CV%) were reported.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 20, 24 hours post-dose on Days 1, 4, and 7
Population: PK set 1 consisted of participants who received at least 1 dose of maribavir, did not vomit within 4 hours post dosing, and had at least 1 evaluable post-dose maribavir concentration value in Part 1. Data for the PK parameters were planned and analyzed based on unique treatment sequence A, B, C. Hence, data was reported separately.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Part 1: Area Under the Curve From the Time of Dosing to the Last Measurable Concentration (AUC0-last) of Maribavir in Plasma | 50.1 Hour*micrograms per milliliter (h*μg/mL) | Geometric Coefficient of Variation 49.21 |
| Treatment B | Part 1: Area Under the Curve From the Time of Dosing to the Last Measurable Concentration (AUC0-last) of Maribavir in Plasma | 41.2 Hour*micrograms per milliliter (h*μg/mL) | Geometric Coefficient of Variation 55.09 |
| Treatment C | Part 1: Area Under the Curve From the Time of Dosing to the Last Measurable Concentration (AUC0-last) of Maribavir in Plasma | 39.1 Hour*micrograms per milliliter (h*μg/mL) | Geometric Coefficient of Variation 60.58 |
90% CI: [73.88, 89.4]ANOVA
90% CI: [70.92, 85.79]ANOVA
Primary
Part 1: Delay Between the Time of Dosing and Time of Appearance of Plasma Concentration (Tlag) of Maribavir in Plasma
Tlag of maribavir in plasma was reported.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 20, 24 hours post-dose on Day 1, 4 and 7
Population: PK set 1 consisted of participants who received at least 1 dose of maribavir, did not vomit within 4 hours post dosing, and had at least 1 evaluable post-dose maribavir concentration value in Part 1. Data for the PK parameters were planned and analyzed based on unique treatment sequence A, B, C. Hence, data was reported separately.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment A | Part 1: Delay Between the Time of Dosing and Time of Appearance of Plasma Concentration (Tlag) of Maribavir in Plasma | 0.00 Hour |
| Treatment B | Part 1: Delay Between the Time of Dosing and Time of Appearance of Plasma Concentration (Tlag) of Maribavir in Plasma | 0.250 Hour |
| Treatment C | Part 1: Delay Between the Time of Dosing and Time of Appearance of Plasma Concentration (Tlag) of Maribavir in Plasma | 0.250 Hour |
Comparison: Statistical analysis of Tlag was performed using a nonparametric test. The median difference of Tlag between treatments and 90% CIs of the median differences were calculated from Hodges-Lehman estimate, and p-value was produced from Wilcoxon signed rank test.p-value: 0.00690% CI: [0.13, 0.25]Wilcoxon signed rank test
Comparison: Statistical analysis of Tlag was performed using a nonparametric test. The median difference of Tlag between treatments and 90% CIs of the median differences were calculated from Hodges-Lehman estimate, and p-value was produced from Wilcoxon signed rank test.p-value: 0.01190% CI: [0.13, 0.25]Wilcoxon signed rank test
Primary
Part 1: Maximum Concentration (Cmax) Occurred at Time of Maximum Observed Concentration Sampled During a Dosing Interval (Tmax) of Maribavir in Plasma
Cmax defined as maximum concentration occurred at tmax of maribavir in plasma was reported. Geometric mean and geometric coefficient of variation percent (CV%) were reported.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 20, 24 hours post-dose on Days 1, 4, and 7
Population: Pharmacokinetic (PK) set 1 consisted of participants who received at least 1 dose of maribavir, did not vomit within 4 hours post dosing, and had at least 1 evaluable post-dose maribavir concentration value in Part 1. Data for the PK parameters were planned and analyzed based on unique treatment sequence A, B, C. Hence, data was reported separately.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Part 1: Maximum Concentration (Cmax) Occurred at Time of Maximum Observed Concentration Sampled During a Dosing Interval (Tmax) of Maribavir in Plasma | 10.7 Micrograms per milliliter (mcg/mL) | Geometric Coefficient of Variation 31.42 |
| Treatment B | Part 1: Maximum Concentration (Cmax) Occurred at Time of Maximum Observed Concentration Sampled During a Dosing Interval (Tmax) of Maribavir in Plasma | 7.35 Micrograms per milliliter (mcg/mL) | Geometric Coefficient of Variation 46.92 |
| Treatment C | Part 1: Maximum Concentration (Cmax) Occurred at Time of Maximum Observed Concentration Sampled During a Dosing Interval (Tmax) of Maribavir in Plasma | 6.84 Micrograms per milliliter (mcg/mL) | Geometric Coefficient of Variation 56.71 |
90% CI: [59.5, 77.16]ANOVA
90% CI: [54.73, 70.9]ANOVA
Primary
Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7
The palatability was evaluated to identify, characterize and quantify the sensory attributes of products, e.g., basic tastes, texture and mouth feel and to assess the overall acceptability. Number of participants responded to palatability assessment up to Day 7 were reported.
Time frame: Up to Day 7
Population: Safety set 1 consisted of all participants who received at least 1 dose of maribavir in Part 1. Data for the palatability was planned and analyzed based on unique treatment sequence A, B, C. Hence, data was reported separately.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment A | Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | Did the drug have a rough or gritty texture?: Yes | 0 Participants |
| Treatment A | Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | How strong was the taste?: Strong | 0 Participants |
| Treatment A | Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | How this drug tasted to you?: Salty | 0 Participants |
| Treatment A | Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | How this drug tasted to you?: Bitter | 2 Participants |
| Treatment A | Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | How strong was the taste?: Medium | 1 Participants |
| Treatment A | Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | Overall taste & texture?: Agree | 18 Participants |
| Treatment A | Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | Did the drug have a rough or gritty texture?: No | 18 Participants |
| Treatment A | Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | How strong was the taste?: Weak | 1 Participants |
| Treatment A | Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | How this drug tasted to you?: Sweet | 0 Participants |
| Treatment A | Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | How strong was the taste?: no taste | 16 Participants |
| Treatment A | Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | Overall taste & texture?: Disagree | 0 Participants |
| Treatment A | Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | Was the drug easy to swallow?: Yes | 18 Participants |
| Treatment A | Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | How this drug tasted to you?: Savory | 0 Participants |
| Treatment A | Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | Overall taste & texture?: Neither agree/disagree | 0 Participants |
| Treatment A | Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | Was the drug easy to swallow?: No | 0 Participants |
| Treatment A | Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | How this drug tasted to you?: No taste | 16 Participants |
| Treatment A | Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | How this drug tasted to you?: Sour | 0 Participants |
| Treatment B | Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | Did the drug have a rough or gritty texture?: No | 4 Participants |
| Treatment B | Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | How this drug tasted to you?: Bitter | 14 Participants |
| Treatment B | Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | How this drug tasted to you?: Salty | 0 Participants |
| Treatment B | Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | How this drug tasted to you?: Sour | 1 Participants |
| Treatment B | Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | How this drug tasted to you?: Sweet | 0 Participants |
| Treatment B | Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | How this drug tasted to you?: Savory | 0 Participants |
| Treatment B | Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | How this drug tasted to you?: No taste | 4 Participants |
| Treatment B | Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | How strong was the taste?: Strong | 8 Participants |
| Treatment B | Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | How strong was the taste?: Medium | 6 Participants |
| Treatment B | Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | How strong was the taste?: Weak | 1 Participants |
| Treatment B | Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | How strong was the taste?: no taste | 4 Participants |
| Treatment B | Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | Did the drug have a rough or gritty texture?: Yes | 15 Participants |
| Treatment B | Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | Was the drug easy to swallow?: No | 0 Participants |
| Treatment B | Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | Was the drug easy to swallow?: Yes | 19 Participants |
| Treatment B | Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | Overall taste & texture?: Agree | 10 Participants |
| Treatment B | Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | Overall taste & texture?: Neither agree/disagree | 5 Participants |
| Treatment B | Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | Overall taste & texture?: Disagree | 4 Participants |
| Treatment C | Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | How this drug tasted to you?: Salty | 1 Participants |
| Treatment C | Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | Did the drug have a rough or gritty texture?: Yes | 16 Participants |
| Treatment C | Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | How this drug tasted to you?: Savory | 0 Participants |
| Treatment C | Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | Overall taste & texture?: Disagree | 3 Participants |
| Treatment C | Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | Was the drug easy to swallow?: No | 0 Participants |
| Treatment C | Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | How this drug tasted to you?: Sweet | 0 Participants |
| Treatment C | Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | Overall taste & texture?: Neither agree/disagree | 4 Participants |
| Treatment C | Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | Was the drug easy to swallow?: Yes | 20 Participants |
| Treatment C | Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | How this drug tasted to you?: Sour | 0 Participants |
| Treatment C | Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | How this drug tasted to you?: Bitter | 14 Participants |
| Treatment C | Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | How strong was the taste?: Weak | 4 Participants |
| Treatment C | Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | Overall taste & texture?: Agree | 13 Participants |
| Treatment C | Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | How strong was the taste?: no taste | 5 Participants |
| Treatment C | Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | How strong was the taste?: Medium | 3 Participants |
| Treatment C | Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | How strong was the taste?: Strong | 8 Participants |
| Treatment C | Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | Did the drug have a rough or gritty texture?: No | 4 Participants |
| Treatment C | Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7 | How this drug tasted to you?: No taste | 5 Participants |
Primary
Part 1: Terminal Half-Life (t1/2) of Maribavir in Plasma
t1/2 of maribavir in plasma was reported.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 20, 24 hours post-dose on Days 1, 4 and 7
Population: PK set 1 consisted of participants who received at least 1 dose of maribavir, did not vomit within 4 hours post dosing, and had at least 1 evaluable post-dose maribavir concentration value in Part 1. Data for the PK parameters were planned and analyzed based on unique treatment sequence A, B, C. Hence, data was reported separately.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment A | Part 1: Terminal Half-Life (t1/2) of Maribavir in Plasma | 4.04 Hour |
| Treatment B | Part 1: Terminal Half-Life (t1/2) of Maribavir in Plasma | 4.80 Hour |
| Treatment C | Part 1: Terminal Half-Life (t1/2) of Maribavir in Plasma | 5.95 Hour |
Primary
Part 1: Time of Maximum Observed Concentration Sampled During a Dosing Interval (Tmax) of Maribavir in Plasma
tmax defined as time of maximum observed concentration sampled during a dosing interval of maribavir in plasma were reported.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 20, 24 hours post-dose on Days 1, 4, and 7
Population: PK set 1 consisted of participants who received at least 1 dose of maribavir, did not vomit within 4 hours post dosing, and had at least 1 evaluable post-dose maribavir concentration value in Part 1. Data for the PK parameters were planned and analyzed based on unique treatment sequence A, B, C. Hence, data was reported separately.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment A | Part 1: Time of Maximum Observed Concentration Sampled During a Dosing Interval (Tmax) of Maribavir in Plasma | 1.00 Hour |
| Treatment B | Part 1: Time of Maximum Observed Concentration Sampled During a Dosing Interval (Tmax) of Maribavir in Plasma | 3.00 Hour |
| Treatment C | Part 1: Time of Maximum Observed Concentration Sampled During a Dosing Interval (Tmax) of Maribavir in Plasma | 2.00 Hour |
Comparison: Statistical analysis of tmax was performed using a nonparametric test. The median difference of tmax between treatments and 90% CIs of the median differences were calculated from Hodges-Lehman estimate, and p-value was produced from Wilcoxon signed rank test.p-value: <0.00190% CI: [0.75, 1.75]Wilcoxon signed rank test
Comparison: Statistical analysis of tmax was performed using a nonparametric test. The median difference of tmax between treatments and 90% CIs of the median differences were calculated from Hodges-Lehman estimate, and p-value was produced from Wilcoxon signed rank test.p-value: <0.00190% CI: [0.75, 1.25]Wilcoxon signed rank test
Secondary
Number of Participants With Clinically Significant Changes in Clinical Laboratory Results Reported as TEAEs
Clinical laboratory tests included biochemistry, hematology and urinalysis. Any change in clinical laboratory results which are deemed clinically significant by the investigator were reported as TEAE.
Time frame: From start of study drug administration up to follow-up (Day 17)
Population: Safety set 1 consisted of all participants who received at least 1 dose of maribavir in Part 1.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment A | Number of Participants With Clinically Significant Changes in Clinical Laboratory Results Reported as TEAEs | 0 Participants |
Secondary
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Reported as TEAEs
12-lead ECG were evaluated. Any change in ECG assessments which are deemed clinically significant by the investigator were reported as TEAE.
Time frame: From start of study drug administration up to follow-up (Day 17)
Population: Safety set 1 consisted of all participants who received at least 1 dose of maribavir in Part 1.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment A | Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Reported as TEAEs | 0 Participants |
Secondary
Number of Participants With Clinically Significant Changes in Vital Signs Reported as TEAEs
Vital sign assessments included systolic and diastolic blood pressure, pulse rate and body temperature. Any change in vital signs which were deemed clinically significant by the investigator were recorded as TEAE.
Time frame: From start of study drug administration up to follow-up (Day 17)
Population: Safety set 1 consisted of all participants who received at least 1 dose of maribavir in Part 1.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment A | Number of Participants With Clinically Significant Changes in Vital Signs Reported as TEAEs | 0 Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily had a causal relationship with this treatment. A TEAE was an adverse event with a start date on or after the first dose of Investigational product (IP), or a start date before the date of the first dose of IP but increased in severity on or after the date of the first dose of IP. Number of participants with TEAEs were reported.
Time frame: From start of study drug administration up to follow-up (Day 17)
Population: Safety Set 1 consisted of all participants who received at least 1 dose of maribavir in Part 1.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment A | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 3 Participants |