| Eligibility |
Inclusion Criteria:
Main Inclusion Criteria:
1. Males or females, of any race, = 18 and = 75 years of age at enrolment
2. Body mass index (BMI) of = 18-40 kg/m2
3. Participants with hepatic impairment:
1. PART 1 and PART 2: Moderate hepatic impairment, as defined by the Child-Pugh
score (Child-Pugh B) [1] who exhibit physical signs consistent with stable
hepatic impairment and free of significant medical disorders unrelated to their
hepatic disorder and are on stable concomitant medication for 2 weeks prior to
and for the duration of this study
2. PART 3: Severe hepatic impairment as defined by the Child-Pugh score (Child Pugh
C) who exhibit physical signs consistent with stable hepatic impairment and free
of significant medical disorders unrelated to their hepatic disorder and are on
stable concomitant medication for 2 weeks prior to and for the duration of this
study
4. Healthy participants (controls) in PART 1 and PART 3:
1. Healthy as determined by the investigator, based on a medical evaluation
including medical history, physical examination, laboratory tests and cardiac
assessment
2. Match at least one of the participants with moderate or severe hepatic impairment
with respect to gender, age (±10 years), and body mass index (BMI) ± 15% (ensure
every participant with hepatic impairment has at least 1 matched control)
5. Women of non-childbearing potential defined as permanently sterile or postmenopausal
6. Males will agree to use contraception throughout the study and until 90-days after the
Follow-up visit
7. Male participants must agree to refrain from sperm donation from the date of
Randomisation (Day 1) until 90 days after the Follow up visit
8. 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)
1. History of an organ transplant, including a remote history of bone marrow transplant
2. History of febrile illness within 7 days prior to the first dose of study drug or
participants with evidence of active infection
3. Use of any oral glucocorticoids at any dose within 30 days prior to Screening and
until study completion
4. Have previously completed or withdrawn from a study investigating GB1211 and have
previously received the investigational product
5. Participant who, in the opinion of the Investigator (or Designee), should not
participate in this study
6. Vulnerable/institutionalised patients
7. Patients related to Principal Investigator (PI)/site staff
8. If female, the participant is of child-bearing potential
9. 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.
10. 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
11. Donation or loss of = 400 mL blood or plasma less than 4 weeks prior to screening, or
longer if required by local regulations
12. Positive HIV test
13. Have received live vaccine(s) within 30 days prior to Screening or who will require a
vaccine(s) and until study completion
14. 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
15. 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
16. 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:
17. Use of any prescription or non-prescription medication (OTC), herbal medication,
dietary supplements or vitamins during 30 days prior to dosing. Acetaminophen is
acceptable
18. 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
19. A positive Hepatitis C test or a positive Hepatitis B surface antigen (HBsAg)
20. 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:
21. 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
22. Estimated glomerular filtration rate (eGFR) < 40 mL/[min*1.73 m²] (estimated using the
[MDRD] equation) at Screening
23. Use of any hepatotoxic drug (e.g. methotrexate, isoniazid, amiodarone) within 30 days
of Screening and until study completion
24. 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
25. 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)
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