Clinical trial NCT04131556: 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
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2019-10-18
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Part 1: Maximum Concentration (Cmax) Occurred at Time of Maximum Observed Concentration Sampled During a Dosing Interval (Tmax) of Maribavir in Plasma
timeFrame: 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
measure: Part 1: Time of Maximum Observed Concentration Sampled During a Dosing Interval (Tmax) of Maribavir in Plasma
timeFrame: 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
measure: Part 1: Area Under the Curve From the Time of Dosing to the Last Measurable Concentration (AUC0-last) of Maribavir in Plasma
timeFrame: 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
measure: Area Under the Curve Extrapolated to Infinity, Calculated Using the Observed Value of the Last Non-Zero Concentration (AUC0-Inf) of Maribavir in Plasma
timeFrame: 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
measure: Part 1: Terminal Half-Life (t1/2) of Maribavir in Plasma
timeFrame: 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
measure: Part 1: Apparent Total Body Clearance Following Extravascular Administration (CL/F) of Maribavir in Plasma
timeFrame: 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
measure: Part 1: Delay Between the Time of Dosing and Time of Appearance of Plasma Concentration (Tlag) of Maribavir in Plasma
timeFrame: 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
measure: Part 1: Number of Participants With Responses to Palatability Assessment up to Day 7
timeFrame: Up to Day 7
Secondary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From start of study drug administration up to follow-up (Day 17)
measure: Number of Participants With Clinically Significant Changes in Vital Signs Reported as TEAEs
timeFrame: From start of study drug administration up to follow-up (Day 17)
measure: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Reported as TEAEs
timeFrame: From start of study drug administration up to follow-up (Day 17)
measure: Number of Participants With Clinically Significant Changes in Clinical Laboratory Results Reported as TEAEs
timeFrame: From start of study drug administration up to follow-up (Day 17)
Other outcomes:
Locations:
city: Miami
country: United States
facility: Clinical Pharmacology of Miami, Llc
state: Florida
Study officials:
affiliation: Shire
name: Study Director
role: STUDY_DIRECTOR
References: