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Safety and Pharmacokinetics Study of Linzagolix in Female Subjects With Normal and Impaired Hepatic Function

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ClinicalTrials.gov Identifier: NCT03962049
Recruitment Status : Recruiting
First Posted : May 23, 2019
Last Update Posted : May 23, 2019
Sponsor:
Information provided by (Responsible Party):
ObsEva SA

Brief Summary:
The primary objective of this study is to assess the pharmacokinetics (PK) of linzagolix in subjects with varying degrees of impaired hepatic function compared to match control subjects with normal hepatic function

Condition or disease Intervention/treatment Phase
Hepatic Impairment Healthy Participants Drug: Linzagolix Phase 1

Detailed Description:

This is a Phase 1, non-randomized, open label, single-dose study to evaluate the effect of varying degrees of impaired hepatic function (i.e., mild, moderate, and severe Hepatic Impairment (HI)) on the PK, safety, and tolerability of linzagolix and its major metabolite, KP017.

Up to 28 adult female participants will be enrolled.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 28 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Evaluation of the Safety and Pharmacokinetics of a Single Dose of Linzagolix in Female Subjects With Normal and Impaired Hepatic Function
Estimated Study Start Date : May 2019
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : October 2019

Arm Intervention/treatment
Experimental: Normal Hepatic Function
Healthy participants with Normal Hepatic Function
Drug: Linzagolix
A single dose of 200 mg linzagolix (2 tablets of 100 mg) will be administered orally under fasting conditions

Experimental: Mild Hepatic Impairment
Presence of Mild Hepatic Impairment (score of 5 to 6, on the Child Pugh scale and with features of cirrhosis due to any etiology)
Drug: Linzagolix
A single dose of 200 mg linzagolix (2 tablets of 100 mg) will be administered orally under fasting conditions

Experimental: Moderate Hepatic Impairment
Presence of Moderate Hepatic Impairment (score of 7 to 9, on the Child Pugh scale and with features of cirrhosis due to any etiology)
Drug: Linzagolix
A single dose of 200 mg linzagolix (2 tablets of 100 mg) will be administered orally under fasting conditions

Experimental: Severe Hepatic Impairment
Presence of Severe Hepatic Impairment (score of 10 to 15 on the Child Pugh scale and with features of cirrhosis due to any etiology)
Drug: Linzagolix
A single dose of 200 mg linzagolix (2 tablets of 100 mg) will be administered orally under fasting conditions




Primary Outcome Measures :
  1. Plasma pharmacokinetic (PK) parameter Cmax of linzagolix and of KP017 [ Time Frame: predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose ]
    Measurement of effect of hepatic impairment on PK of linzagolix and its metabolite KP017 by assessment of the maximum plasma concentration (Cmax). Cmax directly determined from the plasma concentration-time profiles

  2. Plasma PK parameter Tmax of linzagolix and of KP017 [ Time Frame: predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose ]
    Measurement of effect of hepatic impairment on PK of linzagolix and its metabolite KP017 by assessment of the Time to reach Cmax (Tmax)

  3. Plasma PK parameter AUC0-t of linzagolix and of KP017 [ Time Frame: predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose ]
    Measurement of effect of hepatic impairment on PK of linzagolix and its metabolite KP017 by assessment of the AUC0-t (area under the concentration time curve, from time 0 to the last observed non-zero concentration)

  4. Plasma PK parameter T1/2 of linzagolix and of KP017 [ Time Frame: predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose ]
    Measurement of effect of hepatic impairment on PK of linzagolix and its metabolite KP017 by assessment of the T1/2 (Terminal half life)


Secondary Outcome Measures :
  1. Treatment emergent Adverse Events [ Time Frame: Day 1 to 14 days post-dose ]
    Assessment of safety and tolerability of a single dose of linzagolix in hepatic impaired subjects compared with healthy control subjects by assessing the number, frequency and severity of treatment emergent Adverse Events



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Key Inclusion Criteria:

Hepatic Impaired Subjects

  1. Adult female, 18-75 years of age, inclusive, at screening
  2. Has a BMI ≥ 18.0 and ≤ 42.0 kg/m^2 and weight ≥ 40 kg, at screening
  3. Aside from HI, be sufficiently healthy for study participation based upon medical history, physical examination, vital signs, electrocardiograms (ECGs), and screening clinical laboratory profiles, as deemed by the Principal Investigator (PI) or designee
  4. Has a score on the Child-Pugh scale at screening as follows:

    • Severe HI: ≥ 10 and ≤ 15
    • Moderate HI: ≥ 7 and ≤ 9
    • Mild HI: ≥ 5 and ≤ 6
  5. Has a diagnosis of chronic (> 6 months), stable (no acute episodes of illness within the previous 2 months due to deterioration in hepatic function) hepatic insufficiency with features of cirrhosis due to any etiology

Healthy Subjects

  1. Healthy adult female will be matched based upon age and BMI
  2. Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs or ECGs, as deemed by the PI or designee.

Key Exclusion Criteria:

Hepatic Impaired Subjects

  1. Has a clinically active Grade 3 or 4 encephalopathy
  2. Has fluctuating or rapidly deteriorating hepatic function within the screening period, and up to 30 days prior to Day 1, in the opinion of the PI and Sponsor
  3. Has history of liver or other solid organ transplant
  4. Had any major surgery within 4 weeks prior to dosing
  5. Has a surgical (e.g., hepatectomy, nephrectomy, digestive organ resection) or medical condition other than HI which might significantly alter the absorption, distribution, metabolism, or excretion of linzagolix and its metabolites, or which may jeopardize the subject's safety in case of participation in the study in the opinion of the PI or designee

Healthy Subjects

  1. Has any clinically significant illness, as judged by the PI or designee, within 4 weeks prior to dosing
  2. Has laboratory values at screening or check-in which are deemed to be clinically significant (especially derangement within liver function test), unless agreed in advance by the PI and the Sponsor

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): NCT03962049


Contacts
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Contact: Clinical Trial Director +41 (0) 22 552 3840 clinicaltrials@obseva.ch

Locations
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United States, Florida
Clinical Site Recruiting
Hialeah, Florida, United States, 33014
Clinical Site Recruiting
Orlando, Florida, United States, 32809
Sponsors and Collaborators
ObsEva SA
Investigators
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Study Director: ObsEva SA Geneva

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Responsible Party: ObsEva SA
ClinicalTrials.gov Identifier: NCT03962049     History of Changes
Other Study ID Numbers: 18-OBE2109-009
First Posted: May 23, 2019    Key Record Dates
Last Update Posted: May 23, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by ObsEva SA:
Linzagolix
OBE2109
Hepatic Impairment
Hepatic Insufficiency
Liver Diseases
Clinical pharmacology study

Additional relevant MeSH terms:
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Liver Diseases
Digestive System Diseases