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About
This study is a a single (open-label) and repeat dose (randomised, placebo controlled) trial to assess the safety, tolerability and pharmacokinetics of GB1211 (Gal-3 inhibitor) in participants with hepatic impairment (Child Pugh B and Child Pugh C)
Full description
PART 1 A single dose, open-label safety and PK study of GB1211 administered to participants with moderate hepatic impairment (Child Pugh B) and to matched healthy participants (controls).
PART 2 A randomised, double-blind, placebo-controlled study in participants with moderate hepatic impairment (Child Pugh B). GB1211 or placebo will be administered daily for 12 weeks.
PART 3 A single dose, open-label safety and PK study of GB1211 administered to participants with severe hepatic impairment (Child Pugh C) and to healthy participants (controls).
Enrollment
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Inclusion criteria
Main Inclusion Criteria:
Males or females, of any race, ≥ 18 and ≤ 75 years of age at enrolment
Body mass index (BMI) of ≥ 18-40 kg/m2
Participants with hepatic impairment:
Healthy participants (controls) in PART 1 and PART 3:
Women of non-childbearing potential defined as permanently sterile or postmenopausal
Males will agree to use contraception throughout the study and until 90-days after the Follow-up visit
Male participants must agree to refrain from sperm donation from the date of Randomisation (Day 1) until 90 days after the Follow up visit
Able to comprehend and willing to sign an ICF and to abide by the study restrictions
Exclusion criteria
All parts and all groups (control healthy volunteers and hepatic impairment)
History of an organ transplant, including a remote history of bone marrow transplant
History of febrile illness within 7 days prior to the first dose of study drug or participants with evidence of active infection
Use of any oral glucocorticoids at any dose within 30 days prior to Screening and until study completion
Have previously completed or withdrawn from a study investigating GB1211 and have previously received the investigational product
Participant who, in the opinion of the Investigator (or Designee), should not participate in this study
Vulnerable/institutionalised patients
Patients related to Principal Investigator (PI)/site staff
If female, the participant is of child-bearing potential
Participation in a clinical study involving administration of an investigational agent e.g. new chemical entity or a biological product in the past 90 days (or 5 multiples of half-life, whichever is longer) prior to dosing.
Medical history of cardiac disease and/or clinically significant ECG abnormalities. An abnormal ECG is defined as PR > 220 msec, QRS complex >120 msec, QTcF > 450 msec (males) and > 470msec (females), or any other morphological changes, other than nonspecific T-wave changes
Donation or loss of ≥ 400 mL blood or plasma less than 4 weeks prior to screening, or longer if required by local regulations
Positive HIV test
Have received live vaccine(s) within 30 days prior to Screening or who will require a vaccine(s) and until study completion
Use of any medications/products that may inhibit biliary excretion, e.g. bile salt chelators, mycophenolic acid, warfarin, and digoxin, within 30 days prior to Screening and until study completion
Use of any medications/products that may inhibit renal excretion; e.g. cimetidine, pyrimethamine, dolutegravir, probenecid, within 30 days prior to Screening and until study completion
Use of any medications/products that are known inhibitors of P-gp (e.g. clarithromycin, fostamatinib, quinidine, quinine) and inducers of P-gp (e.g. carbmazepine, rifampin, St. John's wort) within 30 days prior to Screening and until study completion
Additional exclusion criteria for matched healthy control subjects:
Use of any prescription or non-prescription medication (OTC), herbal medication, dietary supplements or vitamins during 30 days prior to dosing. Acetaminophen is acceptable
History or presence of liver disease or liver injury as indicated by an abnormal liver function profile such as AST, ALT, alkaline phosphatase, or serum bilirubin
A positive Hepatitis C test or a positive Hepatitis B surface antigen (HBsAg)
Estimated glomerular filtration rate (eGFR) < 80 mL/[min*1.73 m²] (estimated using the Modification of Diet in Renal Disease [MDRD] equation) at Screening
Additional exclusion criteria for hepatic impaired subjects:
Participants meeting any of the following exclusion criteria are not to be enrolled in the study/randomised to treatment:
History of any known serious disease (such as cancer, except skin basal cell carcinomas, major infection, clinically significant gastrointestinal disorder, major autoimmune disease) or other disease which in the Investigator's opinion would exclude the patient from the study
Estimated glomerular filtration rate (eGFR) < 40 mL/[min*1.73 m²] (estimated using the [MDRD] equation) at Screening
Use of any hepatotoxic drug (e.g. methotrexate, isoniazid, amiodarone) within 30 days of Screening and until study completion
Use or intend to use any medications/products known to alter drug absorption, metabolism, or elimination processes, including St. John's Wort, or other putatively hepatoprotective herbal remedies such as milk thistle derivatives, within 30 days prior to dosing, unless deemed acceptable by the Investigator (or Designee). Milk thistle derivates or other hepatoprotective herbal remedies are allowed if stable dose is administered 30 days before dosing
Use or intend to use slow release medications/products considered to still be active within 14 days prior to Randomisation, unless deemed acceptable by the Investigator (or Designee)
Primary purpose
Allocation
Interventional model
Masking
54 participants in 6 patient groups, including a placebo group
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Data sourced from clinicaltrials.gov
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