Study of SHP620 (Maribavir) in Healthy Adults

NCT ID: NCT02775240

Last Updated: 2021-06-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-07-21
• Study Completion Date: 2016-09-12

Brief Summary

The purpose of this study is to determine how an investigational treatment (maribavir) is handled by the body when administered with two already approved drugs (digoxin and dextromethorphan). The study will also look at the safety and tolerability when maribavir is coadministered with digoxin and dextromethorphan versus digoxin and dextromethorphan alone.

Conditions

Cytomegalovirus (CMV)

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Digoxin

On Day 1, subjects will receive a single 0.5 mg (2 x 0.25 mg) oral dose of digoxin.

Group Type: ACTIVE_COMPARATOR

Digoxin

Intervention Type: DRUG

0.5 mg (2 x 0.25 mg) Digoxin oral dose

Maribavir

On Day 8 through Day 15, subjects will receive a 400 mg (2 x 200 mg) BID oral dose of maribavir. Subjects will be given the second dose of maribavir approximately 12 hours after the first dose. On Day 13, subjects will receive a coadministration of a single 0.5 mg (2 x 0.25 mg) oral dose of digoxin and a single 30 mg oral dose of dextromethorphan given with the morning dose of maribavir.

Group Type: EXPERIMENTAL

Digoxin

Intervention Type: DRUG

0.5 mg (2 x 0.25 mg) Digoxin oral dose

Maribavir

Intervention Type: DRUG

200mg twice a day for 8 days

Dextromethorphan

Intervention Type: DRUG

30 mg oral dose

Dextromethorphan

On Day 1, subjects will receive a single 30 mg oral dose of dextromethorphan.

Group Type: ACTIVE_COMPARATOR

Dextromethorphan

Intervention Type: DRUG

30 mg oral dose

Interventions

Digoxin

0.5 mg (2 x 0.25 mg) Digoxin oral dose

Intervention Type: DRUG

Maribavir

200mg twice a day for 8 days

Intervention Type: DRUG

Dextromethorphan

30 mg oral dose

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• An understanding, ability, and willingness to fully comply with study procedures and restrictions.
• Ability to provide written, personally signed, and dated informed consent to participate in the study, before completing any study-related procedures.
• Age 18-50 years, inclusive at the time of consent.
• Subjects must be willing to consent to and provide blood samples for pharmacogenomics analysis.
• Willingness to comply with any applicable contraceptive requirements of the protocol and is:

1. Male, or

2. Female of non-childbearing potential

3. Non-pregnant, non-lactating female

4. Females must be at least 90 days postpartum or nulliparous.

• Must be considered "healthy." Healthy status is defined by absence of evidence of any active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead ECG, hematology, blood chemistry (includes T3, T4, and TSH at screening only), and urinalysis.
• Body mass index (BMI) between 18.5 and 30.0 kg/m2 inclusive.
• Hemoglobin is equal to or greater than 12.0g/dL.
• Ability to swallow a dose of investigational product (which may be multiple tablets at one time or consecutively 1 tablet at a time)

Exclusion Criteria

• Subject has a clinically significant history or a disorder detected during the medical interview/physical examination such as any cardiovascular, broncho-pulmonary, gastrointestinal (eg, inflammatory bowel disease, chronic diarrhea), hepatic, biliary (including gallbladder removal), renal, hematological, endocrine, autoimmune, neurological, or psychiatric disease (including depression) or any other medical condition that is capable of altering the absorption, metabolism, or elimination of drugs; or of constituting a risk factor when taking the investigational product in the judgment of the investigator.
• 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.
• Known history of alcohol or other substance abuse within the last year.
• Donation of blood or blood products (eg, 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:

1. Have used an investigational product (if elimination half-life is <6 days, otherwise 5 half-lives).

2. Have been enrolled in a clinical study (including vaccine studies) that, in the investigator's opinion, may impact this study.

3. Have had any substantial changes in eating habits, as assessed by the investigator.

• Confirmed systolic blood pressure >139 mmHg or <89 mmHg and diastolic blood pressure >89 mmHg or <49 mmHg.
• Twelve-lead ECG demonstrating QTcB >450 msec at screening.
• A positive screen for alcohol or drugs of abuse at screening or Day -1, Period 1.
• Male subjects who consume more than 21 units of alcohol per week or 3 units per day; female subjects who consume more than 14 units of alcohol per week or 2 units per day (1 alcohol unit=1 beer or 1 wine [5 oz/150 mL] or 1 liquor [1.5 oz/40 mL] or 0.75 oz alcohol).
• A positive human immunodeficiency virus, hepatitis B surface antibody, or hepatitis C virus antibody screen.
• Use of tobacco in any form (eg, smoking or chewing) or other nicotine-containing products in any form (eg, gum, patch). Ex-users must report that they have stopped using tobacco for at least 30 days prior to receiving the first dose of investigational product.
• Routine consumption of more than 2 units of caffeine per day or subjects who experience caffeine withdrawal headaches. (One caffeine unit is contained in the following items: one 6 oz [180 mL] cup of coffee, two 12 oz [360 mL] cans of cola, one 12 oz cup of tea, or three 1 oz [85 g] chocolate bars. Decaffeinated coffee, tea, or cola are not considered to contain caffeine.)
• Prior screen failure, randomization, participation, or enrollment in this study or prior enrollment in a clinical study investigating maribavir.
• Current use (defined as use within 14 days prior to the first dose of investigational product) of any medication (including over-the-counter, herbal, or homeopathic preparations [eg, St. John's wort, ginkgo biloba]) with the exception of hormonal replacement therapy and occasional use of ibuprofen and acetaminophen.
• History of sensitivity to heparin or heparin-induced thrombocytopenia.
• Ingestion of known CYP3A modulators within 7 days of Day 1, Period 1 (includes grapefruit or grapefruit juice, oranges, Seville oranges, apples or apple juice, vegetables from the mustard green family [eg, kale, broccoli, watercress, collard greens, kohlrabi, Brussels sprouts, mustard], charbroiled meats, and products containing these ingredients).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Shire

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

Clinical Pharmacology of Miami, Inc.

Miami, Florida, United States

Countries

United States

References

Song IH, Ilic K, Murphy J, Lasseter K, Martin P. Effects of Maribavir on P-Glycoprotein and CYP2D6 in Healthy Volunteers. J Clin Pharmacol. 2020 Jan;60(1):96-106. doi: 10.1002/jcph.1504. Epub 2019 Aug 6.

Reference Type: DERIVED

PMID: 31385617 (View on PubMed)

Other Identifiers

SHP620-115

Identifier Type: -

Identifier Source: org_study_id