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The Effect of Reduced Liver Function on Selatogrel Pharmacokinetics

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04406896
Recruitment Status : Not yet recruiting
First Posted : May 29, 2020
Last Update Posted : June 16, 2020
Sponsor:
Information provided by (Responsible Party):
Idorsia Pharmaceuticals Ltd.

Brief Summary:
This is a prospective, single-center, open-label, single-dose, Phase 1 study, to assess the effect of mild and moderate hepatic impairment due to liver cirrhosis on the pharmacokinetics of selatogrel (ACT-246475).

Condition or disease Intervention/treatment Phase
Healthy Subjects Hepatic Impairment Drug: Selatogrel Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Moderate hepatic impaired participants will be dosed after an interim analysis of at least 6 participants with mild hepatic impairment. Healthy participants will be matched to hepatic impaired participants.
Masking: None (Open Label)
Primary Purpose: Other
Official Title: An Open-label, Single-dose, Phase 1 Study to Evaluate the Pharmacokinetics of Selatogrel in Subjects With Mild and Moderate Hepatic Impairment Compared to Matched Healthy Subjects
Estimated Study Start Date : July 2020
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2020

Arm Intervention/treatment
Experimental: Participants with mild hepatic impairment (Group 1)
Participant with Child-Pugh Grade A Score of 5-6.
Drug: Selatogrel
A single subcutaneous injection of 16 mg.
Other Name: ACT-246475

Experimental: Participants with moderate hepatic impairment (Group 2)
Participant with moderate hepatic impairment with a Child-Pugh Grade B Score of 7-9.
Drug: Selatogrel
A single subcutaneous injection of 16 mg.
Other Name: ACT-246475

Experimental: Healthy participants (Group 3) Drug: Selatogrel
A single subcutaneous injection of 16 mg.
Other Name: ACT-246475




Primary Outcome Measures :
  1. The maximum plasma concentration (Cmax) of selatogrel [ Time Frame: Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 3. ]
  2. Time to reach Cmax (tmax) [ Time Frame: Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 3. ]
  3. Area under the plasma concentration-time curves (AUC0-t) of selatogrel [ Time Frame: Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 3. ]
  4. The area under the plasma concentration-time curve from zero to infinity (AUC0-inf) of selatogrel [ Time Frame: Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 3. ]
  5. Terminal half-life (t½) of selatogrel [ Time Frame: Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 3. ]
  6. The apparent clearance (CL/F) of selatogrel [ Time Frame: Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 3. ]
  7. The apparent volume of distribution (Vz/F) of selatogrel [ Time Frame: Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 3. ]
  8. Plasma protein binding of selatogrel [ Time Frame: Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose and post-dose). ]

Secondary Outcome Measures :
  1. Change from baseline in supine blood pressure [ Time Frame: Multiple predefined times on Day 1 (pre-dose) up to Day 3. ]
  2. Change from baseline in temperature [ Time Frame: Multiple predefined times on Day 1 (pre-dose) up to Day 3. ]
  3. Change from baseline in pulse rate [ Time Frame: Multiple predefined times on Day 1 (pre-dose) up to Day 3. ]
  4. Change from baseline in body weight [ Time Frame: Multiple predefined times on Day 1 (pre-dose) up to Day 3. ]
  5. Change from baseline in clinical laboratory tests [ Time Frame: Multiple predefined times on Day 1 (pre-dose) up to Day 3. ]
  6. Change from baseline at each time point of measurement in ECG variables. [ Time Frame: Multiple predefined times on Day 1 (pre-dose) up to Day 3. ]
  7. Inhibition of platelet aggregation [ Time Frame: Multiple predefined times on Day 1 (pre-dose) up to Day 3. ]


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Ages Eligible for Study:   18 Years to 79 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

All participants (Groups 1,2 and 3)

  • Signed informed consent in a language understandable to the participant prior to any study-mandated procedure.
  • Male or female participant aged between 18 and 79 years (inclusive) at screening.
  • Body mass index of 18.0 to 35.0 kg/m2 (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 (pre-dose). They must consistently and correctly use (from screening, during the entire study, and for at least 30 days after last study treatment administration) an acceptable effective method of contraception method, be sexually inactive, or have a vasectomized partner. If a hormonal contraceptive is used, it must have been initiated at least 1 month before treatment administration.
  • Women of non-childbearing potential.

Additional principal inclusion criteria for participants with hepatic impairment (Groups 1 and 2)

  • Hepatic impairment due to liver cirrhosis according to the Child-Pugh classification:

    • Group 1: Mild hepatic impairment, Child-Pugh A = score 5-6.
    • Group 2: Moderate hepatic impairment, Child-Pugh B = score 7-9.
  • Systolic blood pressure (SBP) 95-160 mmHg, diastolic blood pressure (DBP) 60-95 mmHg, and pulse rate 50-100 bpm (inclusive), measured on the same arm, after 5 minutes in the supine position at screening and on Day 1 (pre-dose).
  • Estimated glomerular filtration rate (eGFR) at screening using the Modification of Diet in Renal Disease (MDRD) formula of:

    • greater than or equal to 60 mL/min/1.73 m2 for participants with mild hepatic impairment (Group 1)
    • greater than or equal to 45 mL/min/1.73 m2 for participants with moderate hepatic impairment (Group 2).
  • Stable concomitant medications for at least 3 weeks prior to screening and up to Day 1 and expected to be stable during the conduct of the study.

Additional principal inclusion criteria for healthy participants (Group 3)

  • Normal blood pressure measured on the same arm, after 5 minutes in the supine position at screening and on Day 1 pre-dose defined as:

    • SBP 90 to 140 mmHg, DBP 60 to 90 mmHg, and pulse rate 50 to 100 bpm (inclusive) for participants less than 60 years of age.
    • SBP 95 to 160 mmHg, DBP 65 to 95 mmHg, and pulse rate 50 to 100 bpm (inclusive) for participants 60 years and older.
  • eGFR greater than or equal to 80 mL/min/1.73 m2 at screening using the MDRD formula.

Exclusion Criteria:

All participants (Groups 1, 2 and 3)

  • Pregnant or lactating woman.
  • Previous exposure to selatogrel.
  • Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.
  • Known hypersensitivity to P2Y12 receptor antagonists or any excipients of the drug formulation.
  • Known platelet disorders.
  • Legal incapacity or limited legal capacity at screening.

Additional exclusion criteria for participants with hepatic impairment (Groups 1 and 2)

  • History or clinical evidence of any disease and/or existence of any surgical or medical condition (e.g., cholecystectomy), which might interfere with the absorption, distribution, metabolism, and excretion (ADME) of the study treatment (except for hepatic impairment, appendectomy, and herniotomy).
  • Acute hepatitis, hepatic cancer, primary biliary cirrhosis, or any form of cholestatic disease.
  • Clinical evidence or suspected acute liver failure as judged by the investigator.
  • Severe ascites and/or pleural effusion.
  • Encephalopathy greater than grade 2.
  • Clinical evidence of current alcohol or drug abuse.
  • Clinically relevant abnormalities on a 12-lead ECG, except for abnormalities related to hepatic impairment, after 5 minutes in the supine position at screening and on Day 1 pre-dose.

Additional exclusion criteria for healthy participants (Group 3)

  • History or clinical evidence of any disease and/or existence of any surgical or medical condition (e.g., cholecystectomy), which might interfere with the ADME of the study treatment (except for appendectomy and herniotomy).
  • History or clinical evidence of alcohol or drug abuse within the 3 years prior to screening.
  • Family or personal history of prolonged bleeding or bleeding disorders, intracranial vascular diseases, stroke, reasonable suspicion of vascular malformations, or peptic ulcers.
  • Previous treatment with any prescribed medications or over-the-counter medications within 2 weeks or 5 times the terminal half-life (t½), whichever is longer prior to study treatment administration (excludes contraceptives and hormone replacement therapy).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04406896


Contacts
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Contact: Clinical Trials Disclosure Desk +41 58 844 1977 clinical-trials-disclosure@idorsia.com

Locations
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Germany
CRS Clinical Research Services
Kiel, Germany, 24105
Sponsors and Collaborators
Idorsia Pharmaceuticals Ltd.
Investigators
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Study Director: Clinical Trials Idorsia Pharmaceuticals Ltd.
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Responsible Party: Idorsia Pharmaceuticals Ltd.
ClinicalTrials.gov Identifier: NCT04406896    
Other Study ID Numbers: ID-076-108
2020-001315-25 ( EudraCT Number )
First Posted: May 29, 2020    Key Record Dates
Last Update Posted: June 16, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Liver Diseases
Digestive System Diseases