Back to resultsA Study to Evaluate the Pharmacokinetics of ACT-541468 in Subjects With Mild, Moderate, and Severe Hepatic Impairment
Primary Purpose
Hepatic Impairment
Status
Completed
Phase
Phase 1
Locations
Switzerland
Study Type
Interventional
Intervention
ACT-541468 25 mg
ACT-541468 25 mg (or 10 mg depending on interim results)
Sponsored by
About this trial
This is an interventional other trial for Hepatic Impairment
Eligibility Criteria
Inclusion Criteria:
- Signed informed consent prior to any study-mandated procedure.
- Male and female subjects aged between 18 and 75 years (inclusive) at screening.
- Women of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test on Day -1. They must consistently and correctly use (from screening, during the entire study, and for at least one month after last study treatment intake) a highly effective method of contraception, be sexually inactive, or have a vasectomized partner.
- Women of non-childbearing potential.
- Body mass index of 18.0 to 35.0 kg/m2 (inclusive) at screening.
For healthy subjects: Normal renal function confirmed by a creatinine clearance at screening according to Cockroft and Gault adjusted to age of:
- ≥ 80 mL/min/1.73 m2 for subjects ≤ 50 years of age.
- ≥ 70 mL/min/1.73 m2 for subjects 51-60 years of age.
- ≥ 60 mL/min/1.73 m2 for subjects 61-75 years of age.
For subjects with hepatic impairment: Degree of liver function impairment due to liver cirrhosis according to the Child-Pugh classification:
- Group A: Mild hepatic impairment, Child-Pugh score 5-6.
- Group B: Moderate hepatic impairment, Child-Pugh score 7-9.
- Group C: Severe hepatic impairment, Child-Pugh score 10-15.
Exclusion Criteria:
- Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.
- For subjects with hepatic impairment: History of major medical or surgical disorders, which, in the opinion of the investigator, are likely to interfere with the absorption, distribution, metabolism, or excretion of the study treatment except for those related to liver cirrhosis (appendectomy and herniotomy allowed, cholecystectomy not allowed).
For healthy subjects:
- History of alcoholism or drug abuse within the 3-year period prior to screening.
- Relevant history of fainting, collapse, syncope, orthostatic hypotension, or vasovagal reactions.
Sites / Locations
- University Hospital Basel
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Group A: ACT-541468 in subjects with mild hepatic impairment
Group B: ACT-541468 in subj. with moderate hepatic impairment
Group C: ACT-541468 in subjects with severe hepatic impairment
Group D: ACT-541468 in healthy subjects.
Arm Description
Single oral dose administered on Day 1.
Single oral dose administered on Day 1.
Single oral dose administered on Day 1.
Single oral dose administered on Day 1.
Outcomes
Primary Outcome Measures
Treatment-emergent adverse events (AEs)
Treatment-emergent serious adverse events (SAEs)
Secondary Outcome Measures
Full Information
NCT ID
NCT03713242
First Posted
October 18, 2018
Last Updated
July 1, 2020
Sponsor
Idorsia Pharmaceuticals Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT03713242
Brief Title
A Study to Evaluate the Pharmacokinetics of ACT-541468 in Subjects With Mild, Moderate, and Severe Hepatic Impairment
Official Title
A Single-center, Open-label, Single-dose, Phase 1 Study to Evaluate the Pharmacokinetics of ACT-541468 in Subjects With Mild, Moderate, and Severe Hepatic Impairment
Study Type
Interventional
2. Study Status
Record Verification Date
July 2020
Overall Recruitment Status
Completed
Study Start Date
February 26, 2018 (Actual)
Primary Completion Date
February 27, 2020 (Actual)
Study Completion Date
February 27, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Idorsia Pharmaceuticals Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a prospective, single-center, open-label, single-dose, Phase 1 study, to assess the effect of mild, moderate, and severe hepatic impairment due to liver cirrhosis on the pharmacokinetics of ACT-541468.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatic Impairment
7. Study Design
Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
prospective, single-center, open-label, single-dose
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
32 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group A: ACT-541468 in subjects with mild hepatic impairment
Arm Type
Experimental
Arm Description
Single oral dose administered on Day 1.
Arm Title
Group B: ACT-541468 in subj. with moderate hepatic impairment
Arm Type
Experimental
Arm Description
Single oral dose administered on Day 1.
Arm Title
Group C: ACT-541468 in subjects with severe hepatic impairment
Arm Type
Experimental
Arm Description
Single oral dose administered on Day 1.
Arm Title
Group D: ACT-541468 in healthy subjects.
Arm Type
Experimental
Arm Description
Single oral dose administered on Day 1.
Intervention Type
Drug
Intervention Name(s)
ACT-541468 25 mg
Intervention Description
Administered as a tablet.
Intervention Type
Drug
Intervention Name(s)
ACT-541468 25 mg (or 10 mg depending on interim results)
Intervention Description
Administered as a tablet.
Primary Outcome Measure Information:
Title
Treatment-emergent adverse events (AEs)
Time Frame
From study treatment administration up to EOS (duration: up to 4 days)
Title
Treatment-emergent serious adverse events (SAEs)
Time Frame
From study treatment administration up to EOS (duration: up to 4 days)
Other Pre-specified Outcome Measures:
Title
Plasma pharmacokinetics: AUC(0-t)
Time Frame
At various timepoints (duration: up to 4 days)
Title
Plasma pharmacokinetics: AUC(0-inf)
Time Frame
At various timepoints (duration: up to 4 days)
Title
Plasma pharmacokinetics: AUC(0-24)
Time Frame
At various timepoints (duration: up to 4 days)
Title
Plasma pharmacokinetics: Cmax
Time Frame
At various timepoints (duration: up to 4 days)
Title
Plasma pharmacokinetics: Tmax
Time Frame
At various timepoints (duration: up to 4 days)
Title
Plasma pharmacokinetics: T1/2
Time Frame
At various timepoints (duration: up to 4 days)
Title
Plasma pharmacokinetics: Cu/C (extent of plasma protein binding)
Time Frame
At various timepoints (duration: up to 4 days)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Signed informed consent prior to any study-mandated procedure.
Male and female subjects aged between 18 and 75 years (inclusive) at screening.
Women of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test on Day -1. They must consistently and correctly use (from screening, during the entire study, and for at least one month after last study treatment intake) a highly effective method of contraception, be sexually inactive, or have a vasectomized partner.
Women of non-childbearing potential.
Body mass index of 18.0 to 35.0 kg/m2 (inclusive) at screening.
For healthy subjects: Normal renal function confirmed by a creatinine clearance at screening according to Cockroft and Gault adjusted to age of:
≥ 80 mL/min/1.73 m2 for subjects ≤ 50 years of age.
≥ 70 mL/min/1.73 m2 for subjects 51-60 years of age.
≥ 60 mL/min/1.73 m2 for subjects 61-75 years of age.
For subjects with hepatic impairment: Degree of liver function impairment due to liver cirrhosis according to the Child-Pugh classification:
Group A: Mild hepatic impairment, Child-Pugh score 5-6.
Group B: Moderate hepatic impairment, Child-Pugh score 7-9.
Group C: Severe hepatic impairment, Child-Pugh score 10-15.
Exclusion Criteria:
Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.
For subjects with hepatic impairment: History of major medical or surgical disorders, which, in the opinion of the investigator, are likely to interfere with the absorption, distribution, metabolism, or excretion of the study treatment except for those related to liver cirrhosis (appendectomy and herniotomy allowed, cholecystectomy not allowed).
For healthy subjects:
History of alcoholism or drug abuse within the 3-year period prior to screening.
Relevant history of fainting, collapse, syncope, orthostatic hypotension, or vasovagal reactions.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Idorsia Pharmaceuticals Ltd.
Official's Role
Study Director
Facility Information:
Facility Name
University Hospital Basel
City
Basel
ZIP/Postal Code
4031
Country
Switzerland
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
34002356
Citation
Berger B, Dingemanse J, Sabattini G, Delahaye S, Duthaler U, Muehlan C, Krahenbuhl S. Effect of Liver Cirrhosis on the Pharmacokinetics, Metabolism, and Tolerability of Daridorexant, A Novel Dual Orexin Receptor Antagonist. Clin Pharmacokinet. 2021 Oct;60(10):1349-1360. doi: 10.1007/s40262-021-01028-8. Epub 2021 May 18.
Results Reference
derived
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A Study to Evaluate the Pharmacokinetics of ACT-541468 in Subjects With Mild, Moderate, and Severe Hepatic Impairment
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