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

Healthy Volunteers Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04131556
• Other study ID #: TAK-620-1019
• Status: Terminated
• Phase: Phase 1
• Start date: October 25, 2019
• Est. completion date: January 6, 2020

Study information

• Verified date: December 2020
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 20
• Est. completion date: January 6, 2020
• Est. primary completion date: January 6, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

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.

Locations

Country	Name	City	State
United States	Clinical Pharmacology of Miami, Llc	Miami	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Shire

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	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
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.	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
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.	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
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.	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
Primary	Part 1: Terminal Half-Life (t1/2) of Maribavir in Plasma	t1/2 of maribavir in plasma was reported.	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
Primary	Part 1: Apparent Total Body Clearance Following Extravascular Administration (CL/F) of Maribavir in Plasma	CL/F of maribavir in Plasma was reported.	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
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.	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
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.	Up to Day 7
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.	From start of study drug administration up to follow-up (Day 17)
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.	From start of study drug administration up to follow-up (Day 17)
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.	From start of study drug administration up to follow-up (Day 17)
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.	From start of study drug administration up to follow-up (Day 17)