An Open-label, Single-dose Study to Assess the Pharmacokinetics of DS-3201b In Subjects With Hepatic Impairment

Daiichi Sankyo3 sites in 1 country28 target enrollmentNovember 21, 2019

ConditionsHepatic Impairment

InterventionsDS-3201b

DrugsDS-3201b

Overview

Phase: Phase 1
Intervention: DS-3201b
Conditions: Hepatic Impairment
Sponsor: Daiichi Sankyo
Enrollment: 28
Locations: 3
Primary Endpoint: Analysis of Pharmacokinetic Parameter: Area under the concentration-time curve up to infinity of DS-3201a (AUCinf)
Status: Completed
Last Updated: 5 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a Phase 1, open-label, parallel design, single-dose pharmacokinetic (PK) study to assess the safety, tolerability, and PK of a single dose of 50 mg of DS-3201b in participants with normal and impaired hepatic function.

Registry

clinicaltrials.gov

Start Date

November 21, 2019

End Date

February 23, 2021

Last Updated

5 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Daiichi Sankyo

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Male and female participants 18 years to 75 years of age (inclusive), with a body mass index (BMI) of 18 kg/m\^2 to 40 kg/m\^2 (inclusive) and body weight between 50 kg and 120 kg (inclusive) at Screening.
•Female participants who are of non-childbearing potential must be:
•Surgically sterile (ie, bilateral tubal ligation or removal of both ovaries and/or uterus at least 6 months prior to dosing, or Essure® with hysterosalpingogram \[documentation to confirm tubal occlusion 12 weeks \[wk\] after procedure\]).
•Naturally postmenopausal (spontaneous cessation of menses) for at least 24 consecutive months prior to dosing, confirmed by follicle stimulating hormone (FSH) or estradiol testing.
•Female participants of childbearing potential with proper means of hormonal and nonhormonal or barrier contraceptive methods; all female participants must have negative pregnancy tests at Screening and Check-in. Female participants must be using proper contraceptive means for at least 1 month prior to Screening. Acceptable means of contraceptive methods include sexual abstinence, vasectomy of male partner, intrauterine device, barrier methods like female condom, diaphragm or cervical cap, spermicide, hormonal contraceptives, or any combination of above. Female participants who normally abstain from sexual activity may be recruited provided that they agree to use a condom and spermicide should they become sexually active at any time during the study and for 90 days post dose. Male partners should also be informed to use a condom during this study period. Participants with hepatic impairment should consult with their primary care physician about using any oral contraceptive options (eg, would a combination of hormonal contraception and barrier contraceptive methods be allowed by the physician).
•Male participants must agree to use a condom and spermicide during sexual intercourse until 90 days post dose or must have had a vasectomy and must be willing not to donate sperm until 90 days post dose. Female partners of male participants should be informed of additional barrier contraceptive during this time and may use barrier and/or hormonal contraceptive methods under the conditions described below. Participants with hepatic impairment should consult with their primary care physician about hormonal contraceptive options for their partner. Participants should use both hormonal and barrier methods of contraception for themselves and their partner.
•Participants must agree to refrain from donation of blood from 56 days prior to Screening, plasma from 2 wk prior to Screening, and platelets from 6 wk prior to Screening. Participants must also agree to refrain from donation of blood until 56 days after the end of study.
•All participants must be willing to refrain from consuming grapefruit/grapefruit juice, Seville oranges, and pomegranates/pomegranate juice 10 days before the study drug is given on Day 1 until End-of-Study.
•Participants with hepatic impairment are required to have:
•Documented history of chronic liver disease diagnosed by ultrasonography, computed tomography scan, liver biopsy, or magnetic resonance imaging or history of chronic (\>6 months) hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.

Exclusion Criteria

•Clinically relevant abnormal history, physical findings, electrocardiogram, or laboratory values at the Screening assessment that could interfere with the objectives of the study or the safety of the participant
•Participants with primary biliary cirrhosis or primary sclerosing cholangitis
•Participants with history of Gilbert's syndrome
•Use of any drugs or substances known to be moderate/strong inhibitors or inducers of CYP3A4 and 3A5 enzymes or P-glycoprotein (P-gp) inhibitors within 14 days or 5 half-lives, if known, of the drugs or substances, whichever is greater, prior to study drug administration
•Receipt of any prescribed or over-the-counter (OTC) systemic, herbal (including St John's wort), or topical medication within 14 days of study drug administration, or any expectation of requiring use of such medication while participating in the study is prohibited
•Presence or history of clinically severe adverse reaction to any drug
•History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (with the exception of appendectomy, hernia repair, and/or cholecystectomy)
•History of any cancer, except non-melanoma skin cancer, or resected non-metastatic cancer with no evidence of disease accepted by the Investigator and Sponsor medical monitor
•A positive drugs of abuse screen from a urine ethanol test (unless the drug is medically prescribed by a licensed health care provider) or alcohol breath test at Screening or at Check-in on Day -2 or a participant who will not agree to smoke ≤10 cigarettes or equivalent per day from Screening up to Enrollment, and is unable to be restricted to ≤5 cigarettes per day and for 6 hours post dose during their period of residence in the clinical unit
•Concomitant use of medications known to affect the elimination of serum creatinine (eg, trimethoprim or cimetidine) and inhibitors of renal tubular secretion (eg, probenecid) within 14 days or 5 half-lives, if known, of the drugs, whichever is greater, prior to study drug administration

Arms & Interventions

Cohort 1: Mild hepatic impairment

Participants who have mild hepatic impairment as assessed by National Cancer Institute Organ Dysfunction Working Group (NCI-ODWG) criteria.

Intervention: DS-3201b

Cohort 2: Moderate hepatic impairment

Participants who have moderate hepatic impairment as assessed by National Cancer Institute Organ Dysfunction Working Group (NCI-ODWG) criteria.

Intervention: DS-3201b

Cohort 3: Healthy participants

Healthy participants who have normal hepatic function with sex, age (±10 years \[y\]), and weight (±20%) matching with the mild and moderate hepatic impairment cohorts.

Intervention: DS-3201b

Outcomes

Primary Outcomes

Analysis of Pharmacokinetic Parameter: Area under the concentration-time curve up to infinity of DS-3201a (AUCinf)