A Study Comparing the Pharmacokinetics and Palatability of Two Candidate Pediatric Powder-for-Oral-Suspension Formulations of Maribavir to the Current Maribavir Tablet Formulation Administered in Healthy Adult Participants

Sponsor
Shire (Industry)
Overall Status
Terminated
CT.gov ID
NCT04131556
Collaborator
(none)
20
Enrollment
1
Location
10
Arms
2.4
Actual Duration (Months)
8.3
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or DiseaseIntervention/TreatmentPhase
Phase 1

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
20 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1, Open-label, Randomized, Crossover, Bioavailability, Dose Proportionality, and Food Effect Study Comparing the Pharmacokinetics and Palatability of Two Candidate Pediatric Powder-for-Oral-Suspension Formulations of Maribavir to the Current Maribavir Tablet Formulation Administered in Healthy Adult Subjects
Actual Study Start Date :
Oct 25, 2019
Actual Primary Completion Date :
Jan 6, 2020
Actual Study Completion Date :
Jan 6, 2020

Arms and Interventions

ArmIntervention/Treatment
Experimental: Part 1: Sequence ABC

Participants will receive 200 milligram (mg) of maribavir tablet orally (Sequence A) on Day 1 followed by 200 mg maribavir powder for oral suspension with 32.5 percent (%) drug loading (Sequence B) on Day 4 followed by maribavir 200 mg powder for oral suspension with 36.1% drug loading (Sequence C) on Day 7 with a washout period of minimum 72 hours and maximum of 73 hours between Day 1, 4 and 7.

Drug: Maribavir
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.
Other Names:
  • TAK620
  • SHP620
  • Experimental: Part 1: Sequence BCA

    Participants will receive 200 mg maribavir powder for oral suspension with 32.5 % drug loading (Sequence B) on Day 1 followed by maribavir 200 mg powder for oral suspension with 36.1% drug loading (Sequence C) on Day 4 and followed by 200 mg of maribavir tablet orally (Sequence A) on Day 7 with a washout period of minimum 72 hours and maximum of 73 hours between Day 1, 4 and 7.

    Drug: Maribavir
    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.
    Other Names:
  • TAK620
  • SHP620
  • Experimental: Part 1: Sequence CAB

    Participants will receive maribavir 200 mg powder for oral suspension with 36.1% drug loading (Sequence C) on Day 1 followed by 200 mg of maribavir tablet orally (Sequence A) on Day 4 and followed by 200 mg maribavir powder for oral suspension with 32.5 % drug loading (Sequence B) on Day 7 with a washout period of minimum 72 hours and maximum of 73 hours between Day 1, 4 and 7.

    Drug: Maribavir
    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.
    Other Names:
  • TAK620
  • SHP620
  • Experimental: Part 1: Sequence CBA

    Participants will receive maribavir 200 mg powder for oral suspension with 36.1% drug loading (Sequence C) on Day 1 followed by 200 mg maribavir powder for oral suspension with 32.5 percent (%) drug loading (Sequence B) on Day 4 and followed by 200 mg of maribavir tablet orally (Sequence A) on Day 7 with a washout period of minimum 72 hours and maximum of 73 hours between Day 1, 4 and 7.

    Drug: Maribavir
    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.
    Other Names:
  • TAK620
  • SHP620
  • Experimental: Part 1: Sequence ACB

    Participants will receive 200 mg of maribavir tablet orally (Sequence A) on Day 1 followed by maribavir 200 mg powder for oral suspension with 36.1% drug loading (Sequence C) on Day 4 and followed by 200 mg maribavir powder for oral suspension with 32.5 % drug loading (Sequence B) on Day 7 with a washout period of minimum 72 hours and maximum of 73 hours between Day 1, 4 and 7.

    Drug: Maribavir
    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.
    Other Names:
  • TAK620
  • SHP620
  • Experimental: Part 1: Sequence BAC

    Participants will receive 200 mg maribavir powder for oral suspension with 32.5 % drug loading (Sequence B) on Day 1 followed by 200 mg of maribavir tablet orally (Sequence A) on Day 4 and followed by maribavir 200 mg powder for oral suspension with 36.1% drug loading (Sequence C) on Day 7 and with a washout period of minimum 72 hours and maximum of 73 hours between Day 1, 4 and 7.

    Drug: Maribavir
    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.
    Other Names:
  • TAK620
  • SHP620
  • Experimental: Part 2: Sequence DEGF

    Participants under fast will receive 50 mg of maribavir powder for oral suspension (Sequence D) on Day 1 followed by 100 mg of maribavir powder for oral suspension (Sequence E) on Day 4 followed by participants feed with a high fat meal will receive 200 mg of maribavir powder for oral suspension (Sequence G) on Day 7 and then followed by participants under fast will receive 200 mg of maribavir powder for oral suspension (Sequence F) on Day 10 with a washout period of minimum 72 hours and maximum of 73 hours between Day 1, 4, 7 and 10. 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.

    Drug: Maribavir
    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.
    Other Names:
  • TAK620
  • SHP620
  • Experimental: Part 2: Sequence EFDG

    Participants under fast will receive 100 mg of maribavir powder for oral suspension (Sequence E) on Day 1 followed by 200 mg of maribavir powder for oral suspension (Sequence F) on Day 4 followed by 50 mg of maribavir powder for oral suspension (Sequence D) on Day 7 and then followed by participants feed with a high fat meal will receive 200 mg of maribavir powder for oral suspension (Sequence G) on Day 10 with a washout period of minimum 72 hours and maximum of 73 hours between Day 1, 4, 7 and 10. 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.

    Drug: Maribavir
    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.
    Other Names:
  • TAK620
  • SHP620
  • Experimental: Part 2: Sequence FGED

    Participants under fast will receive 200 mg of maribavir powder for oral suspension (Sequence F) on Day 1 followed by participants feed with a high fat meal will receive 200 mg of maribavir powder for oral suspension (Sequence G) on Day 4 followed by participants under fast will receive 100 mg of maribavir powder for oral suspension (Sequence E) on Day 7 and then followed by 50 mg of maribavir powder for oral suspension (Sequence D) on Day 10 with a washout period of minimum 72 hours and maximum of 73 hours between Day 1, 4, 7 and 10. 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.

    Drug: Maribavir
    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.
    Other Names:
  • TAK620
  • SHP620
  • Experimental: Part 2: Sequence GDFE

    Participants feed with a high fat meal will receive 200 mg of maribavir powder for oral suspension (Sequence G) on Day 1 followed by participants under fast will receive 50 mg of maribavir powder for oral suspension (Sequence D) on Day 4 followed by 200 mg of maribavir powder for oral suspension (Sequence F) on Day 7 and then followed by 100 mg of maribavir powder for oral suspension (Sequence E) on Day 10 with a washout period of minimum 72 hours and maximum of 73 hours between Day 1, 4, 7 and 10. 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.

    Drug: Maribavir
    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.
    Other Names:
  • TAK620
  • SHP620
  • Outcome Measures

    Primary Outcome Measures

    1. 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.

    2. 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.

    3. 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.

    4. 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.

    5. 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.

    6. 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.

    7. 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.

    8. 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.

    Secondary Outcome Measures

    1. 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.

    2. 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.

    3. 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.

    4. 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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 50 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:
    • An understanding, ability, and willingness to fully comply with study procedures and restrictions.

    • Ability to 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.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Clinical Pharmacology of Miami, LlcMiamiFloridaUnited States33014

    Sponsors and Collaborators

    • Shire

    Investigators

    • Study Director: Study Director, Shire

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Shire
    ClinicalTrials.gov Identifier:
    NCT04131556
    Other Study ID Numbers:
    • TAK-620-1019
    First Posted:
    Oct 18, 2019
    Last Update Posted:
    Jan 19, 2021
    Last Verified:
    Dec 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment DetailsThis 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 DetailThis 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.
    Arm/Group TitleMaribavir
    Arm/Group DescriptionParticipants 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.
    Period Title: Overall Study
    STARTED20
    COMPLETED18
    NOT COMPLETED2

    Baseline Characteristics

    Arm/Group TitleMaribavir
    Arm/Group DescriptionParticipants 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.
    Overall Participants20
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    33.7
    (8.90)
    Sex: Female, Male (Count of Participants)
    Female
    12
    60%
    Male
    8
    40%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    17
    85%
    Not Hispanic or Latino
    3
    15%
    Unknown or Not Reported
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    Asian
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    4
    20%
    White
    16
    80%
    More than one race
    0
    0%
    Unknown or Not Reported
    0
    0%

    Outcome Measures

    1. Primary Outcome
    TitlePart 1: Maximum Concentration (Cmax) Occurred at Time of Maximum Observed Concentration Sampled During a Dosing Interval (Tmax) of Maribavir in Plasma
    DescriptionCmax 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 FramePre-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

    Outcome Measure Data

    Analysis Population Description
    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/Group TitleTreatment ATreatment BTreatment C
    Arm/Group DescriptionParticipants received 200 milligrams (mg) of maribavir tablet orally on Day 1 or Day 4 or Day 7.Participants received 200 mg maribavir powder for oral suspension with 32.5 percent (%) drug loading on Day 1 or Day 4 or Day 7.Participants received maribavir 200 mg powder for oral suspension with 36.1% drug loading on Day 1 or Day 4 or Day 7.
    Measure Participants181920
    Geometric Mean (Geometric Coefficient of Variation) [Micrograms per milliliter (mcg/mL)]
    10.7
    (31.42)
    7.35
    (46.92)
    6.84
    (56.71)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Treatment A, Treatment B
    Comments
    Type of Statistical Test Equivalence
    Comments Equivalence analysis based on confidence intervals (CIs). If the 90% CIs of the geometric mean ratios were within (0.8, 1.25), bioequivalence between the two formulations (test powder for oral suspension versus reference tablet) was to be claimed. A linear mixed effect ANOVA model with treatment, period, sequence as fixed effects and participant within sequence as a random effect was used to fit to ln-transformed PK parameters.
    Statistical Test of Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation Parameter% Ratio of Geometric least square means
    Estimated Value67.76
    Confidence Interval (2-Sided) 90%
    59.50 to 77.16
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Treatment A, Treatment C
    Comments
    Type of Statistical Test Equivalence
    Comments Equivalence analysis based on confidence intervals (CIs). If the 90% CIs of the geometric mean ratios were within (0.8, 1.25), bioequivalence between the two formulations (test powder for oral suspension versus reference tablet) was to be claimed. A linear mixed effect ANOVA model with treatment, period, sequence as fixed effects and participant within sequence as a random effect was used to fit to ln-transformed PK parameters.
    Statistical Test of Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation Parameter% Ratio of Geometric least squares means
    Estimated Value62.29
    Confidence Interval (2-Sided) 90%
    54.73 to 70.90
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Primary Outcome
    TitlePart 1: Time of Maximum Observed Concentration Sampled During a Dosing Interval (Tmax) of Maribavir in Plasma
    Descriptiontmax defined as time of maximum observed concentration sampled during a dosing interval of maribavir in plasma were reported.
    Time FramePre-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

    Outcome Measure Data

    Analysis Population Description
    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/Group TitleTreatment ATreatment BTreatment C
    Arm/Group DescriptionParticipants received 200 milligrams (mg) of maribavir tablet orally on Day 1 or Day 4 or Day 7.Participants received 200 mg maribavir powder for oral suspension with 32.5 percent (%) drug loading on Day 1 or Day 4 or Day 7.Participants received maribavir 200 mg powder for oral suspension with 36.1% drug loading on Day 1 or Day 4 or Day 7.
    Measure Participants181920
    Median (Full Range) [Hour]
    1.00
    3.00
    2.00
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Treatment A, Treatment B
    Comments 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.
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesisp-Value<.001
    Comments
    MethodWilcoxon signed rank test
    Comments
    Method of EstimationEstimation ParameterMedian Difference (Final Values)
    Estimated Value1.25
    Confidence Interval (2-Sided) 90%
    0.75 to 1.75
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Treatment A, Treatment C
    Comments 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.
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesisp-Value<.001
    Comments
    MethodWilcoxon signed rank test
    Comments
    Method of EstimationEstimation ParameterMedian Difference (Final Values)
    Estimated Value1.00
    Confidence Interval (2-Sided) 90%
    0.75 to 1.25
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Primary Outcome
    TitlePart 1: Area Under the Curve From the Time of Dosing to the Last Measurable Concentration (AUC0-last) of Maribavir in Plasma
    DescriptionAUC0-last of maribavir in plasma was reported. Geometric mean and geometric coefficient of variation percent (CV%) were reported.
    Time FramePre-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

    Outcome Measure Data

    Analysis Population Description
    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/Group TitleTreatment ATreatment BTreatment C
    Arm/Group DescriptionParticipants received 200 milligrams (mg) of maribavir tablet orally on Day 1 or Day 4 or Day 7.Participants received 200 mg maribavir powder for oral suspension with 32.5 percent (%) drug loading on Day 1 or Day 4 or Day 7.Participants received maribavir 200 mg powder for oral suspension with 36.1% drug loading on Day 1 or Day 4 or Day 7.
    Measure Participants181920
    Geometric Mean (Geometric Coefficient of Variation) [Hour*micrograms per milliliter (h*μg/mL)]
    50.1
    (49.21)
    41.2
    (55.09)
    39.1
    (60.58)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Treatment A, Treatment B
    Comments
    Type of Statistical Test Equivalence
    Comments Equivalence analysis based on confidence intervals (CIs). If the 90% CIs of the geometric mean ratios were within (0.8, 1.25), bioequivalence between the two formulations (test powder for oral suspension versus reference tablet) was to be claimed. A linear mixed effect ANOVA model with treatment, period, sequence as fixed effects and participant within sequence as a random effect was used to fit to ln-transformed PK parameters.
    Statistical Test of Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation Parameter% Ratio of Geometric least squares means
    Estimated Value81.27
    Confidence Interval (2-Sided) 90%
    73.88 to 89.40
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Treatment A, Treatment C
    Comments
    Type of Statistical Test Equivalence
    Comments Equivalence analysis based on confidence intervals (CIs). If the 90% CIs of the geometric mean ratios were within (0.8, 1.25), bioequivalence between the two formulations (test powder for oral suspension versus reference tablet) was to be claimed. A linear mixed effect ANOVA model with treatment, period, sequence as fixed effects and participant within sequence as a random effect was used to fit to ln-transformed PK parameters.
    Statistical Test of Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation Parameter% Ratio of Geometric least squares means
    Estimated Value78.00
    Confidence Interval (2-Sided) 90%
    70.92 to 85.79
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Primary Outcome
    TitleArea Under the Curve Extrapolated to Infinity, Calculated Using the Observed Value of the Last Non-Zero Concentration (AUC0-Inf) of Maribavir in Plasma
    DescriptionAUC0-Inf of maribavir in plasma was reported. Geometric mean and geometric coefficient of variation percent (CV%) were reported.
    Time FramePre-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

    Outcome Measure Data

    Analysis Population Description
    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/Group TitleTreatment ATreatment BTreatment C
    Arm/Group DescriptionParticipants received 200 milligrams (mg) of maribavir tablet orally on Day 1 or Day 4 or Day 7.Participants received 200 mg maribavir powder for oral suspension with 32.5 percent (%) drug loading on Day 1 or Day 4 or Day 7.Participants received maribavir 200 mg powder for oral suspension with 36.1% drug loading on Day 1 or Day 4 or Day 7.
    Measure Participants181920
    Geometric Mean (Geometric Coefficient of Variation) [h*μg/mL]
    52.5
    (49.72)
    44.5
    (56.26)
    42.4
    (60.69)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Treatment A, Treatment B
    Comments
    Type of Statistical Test Equivalence
    Comments Equivalence analysis based on confidence intervals (CIs). If the 90% CIs of the geometric mean ratios were within (0.8, 1.25), bioequivalence between the two formulations (test powder for oral suspension versus reference tablet) was to be claimed. A linear mixed effect ANOVA model with treatment, period, sequence as fixed effects and participant within sequence as a random effect was used to fit to ln-transformed PK parameters.
    Statistical Test of Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation Parameter% Ratio of Geometric least squares means
    Estimated Value83.52
    Confidence Interval (2-Sided) 90%
    76.12 to 91.64
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Treatment A, Treatment C
    Comments
    Type of Statistical Test Equivalence
    Comments Equivalence analysis based on confidence intervals (CIs). If the 90% CIs of the geometric mean ratios were within (0.8, 1.25), bioequivalence between the two formulations (test powder for oral suspension versus reference tablet) was to be claimed. A linear mixed effect ANOVA model with treatment, period, sequence as fixed effects and participant within sequence as a random effect was used to fit to ln-transformed PK parameters.
    Statistical Test of Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation Parameter% Ratio of Geometric least squares means
    Estimated Value80.36
    Confidence Interval (2-Sided) 90%
    73.26 to 88.16
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Primary Outcome
    TitlePart 1: Terminal Half-Life (t1/2) of Maribavir in Plasma
    Descriptiont1/2 of maribavir in plasma was reported.
    Time FramePre-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

    Outcome Measure Data

    Analysis Population Description
    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/Group TitleTreatment ATreatment BTreatment C
    Arm/Group DescriptionParticipants received 200 milligrams (mg) of maribavir tablet orally on Day 1 or Day 4 or Day 7.Participants received 200 mg maribavir powder for oral suspension with 32.5 percent (%) drug loading on Day 1 or Day 4 or Day 7.Participants received maribavir 200 mg powder for oral suspension with 36.1% drug loading on Day 1 or Day 4 or Day 7.
    Measure Participants181920
    Median (Full Range) [Hour]
    4.04
    4.80
    5.95
    6. Primary Outcome
    TitlePart 1: Apparent Total Body Clearance Following Extravascular Administration (CL/F) of Maribavir in Plasma
    DescriptionCL/F of maribavir in Plasma was reported.
    Time FramePre-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

    Outcome Measure Data

    Analysis Population Description
    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/Group TitleTreatment ATreatment BTreatment C
    Arm/Group DescriptionParticipants received 200 milligrams (mg) of maribavir tablet orally on Day 1 or Day 4 or Day 7.Participants received 200 mg maribavir powder for oral suspension with 32.5 percent (%) drug loading on Day 1 or Day 4 or Day 7.Participants received maribavir 200 mg powder for oral suspension with 36.1% drug loading on Day 1 or Day 4 or Day 7.
    Measure Participants181920
    Mean (Standard Deviation) [Liters per hour (L/h)]
    4.21
    (1.99)
    5.13
    (2.82)
    5.49
    (3.29)
    7. Primary Outcome
    TitlePart 1: Delay Between the Time of Dosing and Time of Appearance of Plasma Concentration (Tlag) of Maribavir in Plasma
    DescriptionTlag of maribavir in plasma was reported.
    Time FramePre-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

    Outcome Measure Data

    Analysis Population Description
    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/Group TitleTreatment ATreatment BTreatment C
    Arm/Group DescriptionParticipants received 200 milligrams (mg) of maribavir tablet orally on Day 1 or Day 4 or Day 7.Participants received 200 mg maribavir powder for oral suspension with 32.5 percent (%) drug loading on Day 1 or Day 4 or Day 7.Participants received maribavir 200 mg powder for oral suspension with 36.1% drug loading on Day 1 or Day 4 or Day 7.
    Measure Participants181920
    Median (Full Range) [Hour]
    0.00
    0.250
    0.250
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Treatment A, Treatment B
    Comments 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.
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesisp-Value0.006
    Comments
    MethodWilcoxon signed rank test
    Comments
    Method of EstimationEstimation ParameterMedian Difference (Final Values)
    Estimated Value0.13
    Confidence Interval (2-Sided) 90%
    0.13 to 0.25
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Treatment A, Treatment C
    Comments 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.
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesisp-Value0.011
    Comments
    MethodWilcoxon signed rank test
    Comments
    Method of EstimationEstimation ParameterMedian Difference (Final Values)
    Estimated Value0.13
    Confidence Interval (2-Sided) 90%
    0.13 to 0.25
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    8. Primary Outcome
    TitlePart 1: Number of Participants With Responses to Palatability Assessment up to Day 7
    DescriptionThe 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 FrameUp to Day 7

    Outcome Measure Data

    Analysis Population Description
    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/Group TitleTreatment ATreatment BTreatment C
    Arm/Group DescriptionParticipants received 200 milligrams (mg) of maribavir tablet orally on Day 1 or Day 4 or Day 7.Participants received 200 mg maribavir powder for oral suspension with 32.5 percent (%) drug loading on Day 1 or Day 4 or Day 7.Participants received maribavir 200 mg powder for oral suspension with 36.1% drug loading on Day 1 or Day 4 or Day 7.
    Measure Participants181920
    How this drug tasted to you?: Bitter
    2
    10%
    14
    NaN
    14
    NaN
    How this drug tasted to you?: Salty
    0
    0%
    0
    NaN
    1
    NaN
    How this drug tasted to you?: Sour
    0
    0%
    1
    NaN
    0
    NaN
    How this drug tasted to you?: Sweet
    0
    0%
    0
    NaN
    0
    NaN
    How this drug tasted to you?: Savory
    0
    0%
    0
    NaN
    0
    NaN
    How this drug tasted to you?: No taste
    16
    80%
    4
    NaN
    5
    NaN
    How strong was the taste?: Strong
    0
    0%
    8
    NaN
    8
    NaN
    How strong was the taste?: Medium
    1
    5%
    6
    NaN
    3
    NaN
    How strong was the taste?: Weak
    1
    5%
    1
    NaN
    4
    NaN
    How strong was the taste?: no taste
    16
    80%
    4
    NaN
    5
    NaN
    Did the drug have a rough or gritty texture?: No
    18
    90%
    4
    NaN
    4
    NaN
    Did the drug have a rough or gritty texture?: Yes
    0
    0%
    15
    NaN
    16
    NaN
    Was the drug easy to swallow?: No
    0
    0%
    0
    NaN
    0
    NaN
    Was the drug easy to swallow?: Yes
    18
    90%
    19
    NaN
    20
    NaN
    Overall taste & texture?: Agree
    18
    90%
    10
    NaN
    13
    NaN
    Overall taste & texture?: Neither agree/disagree
    0
    0%
    5
    NaN
    4
    NaN
    Overall taste & texture?: Disagree
    0
    0%
    4
    NaN
    3
    NaN
    9. Secondary Outcome
    TitleNumber of Participants With Treatment-Emergent Adverse Events (TEAEs)
    DescriptionAn 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 FrameFrom start of study drug administration up to follow-up (Day 17)

    Outcome Measure Data

    Analysis Population Description
    Safety Set 1 consisted of all participants who received at least 1 dose of maribavir in Part 1.
    Arm/Group TitleMaribavir
    Arm/Group DescriptionParticipants 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.
    Measure Participants20
    Count of Participants [Participants]
    3
    15%
    10. Secondary Outcome
    TitleNumber of Participants With Clinically Significant Changes in Vital Signs Reported as TEAEs
    DescriptionVital 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 FrameFrom start of study drug administration up to follow-up (Day 17)

    Outcome Measure Data

    Analysis Population Description
    Safety set 1 consisted of all participants who received at least 1 dose of maribavir in Part 1.
    Arm/Group TitleMaribavir
    Arm/Group DescriptionParticipants 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.
    Measure Participants20
    Count of Participants [Participants]
    0
    0%
    11. Secondary Outcome
    TitleNumber of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Reported as TEAEs
    Description12-lead ECG were evaluated. Any change in ECG assessments which are deemed clinically significant by the investigator were reported as TEAE.
    Time FrameFrom start of study drug administration up to follow-up (Day 17)

    Outcome Measure Data

    Analysis Population Description
    Safety set 1 consisted of all participants who received at least 1 dose of maribavir in Part 1.
    Arm/Group TitleMaribavir
    Arm/Group DescriptionParticipants 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.
    Measure Participants18
    Count of Participants [Participants]
    0
    0%
    12. Secondary Outcome
    TitleNumber of Participants With Clinically Significant Changes in Clinical Laboratory Results Reported as TEAEs
    DescriptionClinical 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 FrameFrom start of study drug administration up to follow-up (Day 17)

    Outcome Measure Data

    Analysis Population Description
    Safety set 1 consisted of all participants who received at least 1 dose of maribavir in Part 1.
    Arm/Group TitleMaribavir
    Arm/Group DescriptionParticipants 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.
    Measure Participants18
    Count of Participants [Participants]
    0
    0%

    Adverse Events

    Time FrameFrom start of study drug administration up to follow-up (Day 17)
    Adverse Event Reporting Description
    Arm/Group TitleMaribavir
    Arm/Group DescriptionParticipants 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.
    All Cause Mortality
    Maribavir
    Affected / at Risk (%)# Events
    Total0/20 (0%)
    Serious Adverse Events
    Maribavir
    Affected / at Risk (%)# Events
    Total0/20 (0%)
    Other (Not Including Serious) Adverse Events
    Maribavir
    Affected / at Risk (%)# Events
    Total3/20 (15%)
    Gastrointestinal disorders
    Flatulence1/20 (5%) 1
    Investigations
    Liver function test increased1/20 (5%) 1
    Nervous system disorders
    Headache1/20 (5%) 1

    Limitations/Caveats

    Sponsor terminated this study based on the planned interim analysis of the data of Part 1, palatability of both pediatric formulations was not acceptable.

    More Information

    Certain Agreements

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

    If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.

    Results Point of Contact

    Name/TitleStudy Director
    OrganizationShire
    Phone+1 866 842 5335
    EmailClinicalTransparency@shire.com
    Responsible Party:
    Shire
    ClinicalTrials.gov Identifier:
    NCT04131556
    Other Study ID Numbers:
    • TAK-620-1019
    First Posted:
    Oct 18, 2019
    Last Update Posted:
    Jan 19, 2021
    Last Verified:
    Dec 1, 2020