Hepatic ImpairmentPhase 1NCT04276662
Study of Single-dose DS-3201b in Participants With Hepatic Impairment
A Phase 1 study testing DS-3201b in people with Hepatic Impairment, run by Daiichi Sankyo at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Hepatic Impairment
- What is being tested?
- DS-3201b
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 3 sitesUnited States
- Study dates
- 21 Nov 2019to 23 Feb 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
- Hepatic impairment as assessed by NCI-ODWG classification 2
- Mild hepatic impairment as assessed by:
- Total bilirubin (Tbil) ≤upper limit of normal (ULN) and AST >ULN, or
- Tbil >1 to 1.5 × ULN (not due to Gilbert's syndrome)
- OR
- Moderate hepatic impairment as assessed by:
- Tbil >1.5 to 3 × ULN (not due to Gilbert's syndrome)
- Physical examination findings that are normal or not clinically significant and clinical laboratory evaluations with normal limits or not clinically significant deviations, with exception of findings that in the opinion of the investigator are consistent with the participant's hepatic impairment
- Clinical stability in the opinion of the investigator. No evidence of active HBV and/or new or acute HCV infection within the preceding 6 months.
- Estimated creatinine clearance (CrCl) ≥60 mL/min by Cockcroft-Gault equation at Screening and Check-in
Who cannot join
- 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
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- 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
- History or presence of an abnormal electrocardiogram, which, in the investigator's opinion, is clinically significant and/or a QT interval corrected for heart rate using Fridericia's formula ≥450 milliseconds (ms) and ≥470 ms for healthy male and female participants, respectively, and >500 ms for subjects with hepatic impairment at Screening
- Consumption of alcohol- and caffeine-containing beverages within 72 hours prior to Check-in and during confinement
- History of moderate to heavy alcohol use defined as consumption of more than 28 units of alcohol per week for males or 14 units of alcohol per week for females, where 1 unit of alcohol equals one-half pint of beer, 4 ounces (oz) of wine, or 1 oz of spirits, or significant history of alcoholism or drug/chemical abuse within the last 2 years
- Positive serology for hepatitis B surface antigen (HBsAg) and HCV (healthy participants), hepatitis A virus (HAV) immunoglobulin M, or anti-human immunodeficiency virus (HIV) Type 1 and Type 2 (participants)
- Loss of more than 450 mL blood during the 3 months before the trial (eg, as a blood donor)
- Current enrollment in or have not yet completed at least 30 days or 5 elimination half-lives, whichever is longer, since receiving an investigational device or product, or receipt of other investigational agents within 30 days of DS-3201b
- In the opinion of the investigator, history of a clinically significant illness within 4 wk prior to administration of study drug
- Women of childbearing potential without proper nonhormonal or barrier contraceptive measures and women who are pregnant or breastfeeding. Male and female participants may be excluded from the study if the primary investigator at the site forbids specific methods of contraception they are using.
- Start of any new medication or any changes to a current dosage within 14 days prior to study drug administration excluding approved oral contraceptives
- Additional Exclusion Criteria for Matched Healthy Participants:
- Any clinically relevant abnormality identified on the physical examination, electrocardiogram, vital signs, or laboratory tests at Screening
- Liver function (aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase (ALP) of liver origin, gamma glutamyltransferase [GGT], and Total bilirubin [TBil]) test results above the ULN at Screening and during Enrollment on Day -2 are exclusionary. If transaminase levels are >2 × ULN at Screening the participant will be excluded and cannot be rescreened
- Additional Exclusion Criteria for Participants with Hepatic Impairment:
- Participants with active stage 3 or stage 4 encephalopathy
- Fluctuating or rapidly deteriorating hepatic function as indicated by recent history or worsening of clinical and/or laboratory signs of hepatic impairment as judged by the investigator
- Participants with known portal hypertension and/or had shunting procedures done
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Clinical Pharmacology of Miami, LLC
Miami, Florida, 33014
Orlando Clinical Research Center
Orlando, Florida, 32809
Worldwide Clinical Trials
San Antonio, Texas, 78217
About this study
Official title: An Open-label, Single-dose Study to Assess the Pharmacokinetics of DS-3201b In Subjects With Hepatic Impairment
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.
- Conditions
- Hepatic Impairment
- Being tested
- DS-3201b
- Keywords
- Hepatic Impairment, DS-3201b, Enhancer of zeste homolog (EZH) inhibitor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DS-3201bDrug
1 dose of 50 mg DS-3201b
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: Mild hepatic impairment | Experimental | Participants who have mild hepatic impairment as assessed by National Cancer Institute Organ Dysfunction Working Group (NCI-ODWG) criteria. Receives: Drug: DS-3201b |
| Cohort 2: Moderate hepatic impairment | Experimental | Participants who have moderate hepatic impairment as assessed by National Cancer Institute Organ Dysfunction Working Group (NCI-ODWG) criteria. Receives: Drug: DS-3201b |
| Cohort 3: Healthy participants | Experimental | 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. Receives: Drug: DS-3201b |
What is being measured
The primary outcome is the main question the study is designed to answer.
Analysis of Pharmacokinetic Parameter: Maximum Concentration of DS-3201a (Cmax)
Cmax is the maximum concentration of DS-3201a in plasma
Measured: 1 to 10 days postdose
Analysis of Pharmacokinetic Parameter: Area under the concentration-time curve from time zero to time of last measurable concentration of DS-3201a (AUClast)
AUClast is the area under the concentration-time curve from time zero to time of last measurable concentration of DS-3201a in plasma
Measured: 1 to 10 days postdose
Analysis of Pharmacokinetic Parameter: Area under the concentration-time curve up to infinity of DS-3201a (AUCinf)
AUCinf is the area under the concentration-time curve up to infinity of DS-3201a in plasma
Measured: 1 to 10 days postdose
Analysis of Pharmacokinetic Parameter: Time to reach maximum concentration of DS-3201a (Tmax)
Tmax is the time to reach maximum concentration of DS-3201a in plasma
Measured: 1 to 10 days postdose
Analysis of Pharmacokinetic Parameter: Apparent total body clearance of DS-3201a (CL/F)
CL/F is the apparent total body clearance of DS-3201a in plasma
Measured: 1 to 10 days postdose
Analysis of Pharmacokinetic Parameter: Apparent volume of distribution of DS-3201a (Vz/F)
Vz/F is the apparent volume of distribution of DS-3201a in plasma
Measured: 1 to 10 days postdose
Analysis of Pharmacokinetic Parameter: Terminal elimination half-life of DS-3201a (t1/2)
t1/2 is the terminal elimination half-life of DS-3201a in plasma
Measured: 1 to 10 days postdose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2020
- Study start21 Nov 2019
- Primary completion23 Feb 2021
- Study completion23 Feb 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatic ImpairmentStudies of the same condition, open and under way.
- More trials run by Daiichi SankyoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Phase 1, open-label, parallel design, single-dose PK study
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Daiichi Sankyo
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Global Clinical Leader, Study director, Daiichi Sankyo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04276662
- Sponsor's protocol ID
- DS3201-A-U106
- Status last verified
- Feb 2021
- First submitted
- 17 Feb 2020
- Last updated
- 25 Feb 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Single-dose Study to Assess the Pharmacokinetics of DS-3201b In Subjects With Hepatic Impairment
- ClinicalTrials.gov ID
- NCT04276662
- Acronym / sponsor ID
- DS3201-A-U106
- Conditions
- Hepatic Impairment
- Keywords
- Hepatic Impairment, DS-3201b, Enhancer of zeste homolog (EZH) inhibitor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Daiichi SankyoIndustry (pharma, biotech, devices)
- Study start
- 21 Nov 2019 (actual)
- Primary completion
- 23 Feb 2021 (actual)
- Study completion
- 23 Feb 2021 (actual)
- First posted
- 19 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Phase 1, open-label, parallel design, single-dose PK study
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: Mild hepatic impairment | Experimental | Drug: DS-3201bParticipants who have mild hepatic impairment as assessed by National Cancer Institute Organ Dysfunction Working Group (NCI-ODWG) criteria. |
| Cohort 2: Moderate hepatic impairment | Experimental | Drug: DS-3201bParticipants who have moderate hepatic impairment as assessed by National Cancer Institute Organ Dysfunction Working Group (NCI-ODWG) criteria. |
| Cohort 3: Healthy participants | Experimental | Drug: DS-3201bHealthy participants who have normal hepatic function with sex, age (±10 years [y]), and weight (±20%) matching with the mild and moderate hepatic impairment cohorts. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- 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).
Key exclusion criteria (26 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DS-3201b1 dose of 50 mg DS-3201b | Drug | Cohort 1: Mild hepatic impairment, Cohort 2: Moderate hepatic impairment, Cohort 3: Healthy participants |
Primary outcome
Analysis of Pharmacokinetic Parameter: Maximum Concentration of DS-3201a (Cmax)
Time frame: 1 to 10 days postdose
Cmax is the maximum concentration of DS-3201a in plasma
Analysis of Pharmacokinetic Parameter: Area under the concentration-time curve from time zero to time of last measurable concentration of DS-3201a (AUClast)
Time frame: 1 to 10 days postdose
AUClast is the area under the concentration-time curve from time zero to time of last measurable concentration of DS-3201a in plasma
Analysis of Pharmacokinetic Parameter: Area under the concentration-time curve up to infinity of DS-3201a (AUCinf)
Time frame: 1 to 10 days postdose
AUCinf is the area under the concentration-time curve up to infinity of DS-3201a in plasma
Analysis of Pharmacokinetic Parameter: Time to reach maximum concentration of DS-3201a (Tmax)
Time frame: 1 to 10 days postdose
Tmax is the time to reach maximum concentration of DS-3201a in plasma
Analysis of Pharmacokinetic Parameter: Apparent total body clearance of DS-3201a (CL/F)
Time frame: 1 to 10 days postdose
CL/F is the apparent total body clearance of DS-3201a in plasma
Analysis of Pharmacokinetic Parameter: Apparent volume of distribution of DS-3201a (Vz/F)
Time frame: 1 to 10 days postdose
Vz/F is the apparent volume of distribution of DS-3201a in plasma
Analysis of Pharmacokinetic Parameter: Terminal elimination half-life of DS-3201a (t1/2)
Time frame: 1 to 10 days postdose
t1/2 is the terminal elimination half-life of DS-3201a in plasma
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Feb 2021.
- Individual participant dataSharing planned: Yes. De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Global Clinical Leader study director
Daiichi Sankyo
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing DS-3201b in people with Hepatic Impairment, run by Daiichi Sankyo at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Analysis of Pharmacokinetic Parameter: Maximum Concentration of DS-3201a (Cmax) (time frame: 1 to 10 days postdose). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Feb 2021.