Multiple Ascending Dose Study of GMC-252-L-Lys Salt in Healthy Subjects and Type 2 Diabetics
Healthy, Type 2 Diabetes Mellitus
About this trial
This is an interventional treatment trial for Healthy
Eligibility Criteria
Inclusion Criteria
Part 1 (Healthy Subjects) and Part 2 (Type 2 Diabetic Patients):
- Diet: Able to eat standard food, no vegetarians.
- Compliance: Understands and is willing, able and likely to comply with all study procedures and restrictions.
- Consent: Demonstrates understanding of the study and has given signed, voluntary written informed consent.
- Have no known hypersensitivity to diflunisal, NAC or other NSAIDs.
- No history of blood diseases including but not limited to clinically significant platelet diseases and coagulation abnormalities.
- No clinically relevant gastrointestinal disease.
- Have an estimated creatinine (CREA) clearance>70 mL/min/surface area (CREA clearance will be calculated from the serum CREA value by using the Cockroft and Gault formula).
- Have no history of heart failure or uncontrolled hypertension or other known clinically significant cardiovascular disease.
- Have no history of bronchial asthma or 'Aspirin Triad' (chronic rhino-sinusitis with polyps, severe asthma and intolerance to aspirin or other NSAIDs).
- Have no clinically significant abnormality of liver tests before entry into the study.
- A negative urinary drugs of abuse screen, determined within 28 days before the first dose (N.B. a positive alcohol result may be repeated at the discretion of the Investigator).
- Negative human immunodeficiency virus (HIV) and hepatitis B surface antigen (Hep B) and hepatitis C virus antibody (Hep C) results.
- No clinically significant abnormalities in a 12-lead ECG determined within 28 days before the first dose.
- No history of clinically significant renal disease or any food intolerance.
- Willing to use 2 effective methods of contraception i.e. established method of contraception + condom, if applicable (unless anatomically sterile or where abstaining from sexual intercourse is in line with the preferred and usual lifestyle of the subject) from Day 1 until 3 months afterwards.
Additional Criteria for Part 1 (Healthy Subjects):
- Healthy males aged 18 to 55 inclusive.
- Body mass index (BMI) within the range of 18-30 kg/m2 inclusive.
- Non-Smokers (including e-cigarettes) who have abstained from smoking for at least 6 months.
Additional Criteria for Part 2 (Type 2 Diabetic Patients):
- Males aged 18 to 65 inclusive. BMI within the range of 18-38 kg/m2 inclusive.
- Diagnosis of T2DM according to the World Health Organization criteria.
- HbA1c between 7.0% and 12.0 % inclusive.
- Currently treated with metformin with a stable treatment regimen for 3 months or more prior to the Screening Visit, and not receiving other anti-diabetic medications. Allowed medication during the study include metformin, statin (3-hydroxy-3-methylglutaryl-coenzyme A (HMG CoA) reductase inhibitors), paracetamol up to 3 g/day, low doses of aspirin and antihypertensive drugs if the doses are not changed in the 3 months before the start of screening. Other allowed medications will be approved by PI and Sponsor before a patient can be enrolled. Diflunisal (a test drug component) may decrease the antihypertensive activityof many of the currently used antihypertensive medications, such as β-blockers, alpha (α)-blockers, loop diuretics, angiotensin converting enzyme (ACE inhibitors), angiotensin 2 receptor blockers, calcium channel blockers. Therefore, patients who are on current stable antihypertensive medications will be subjected to close monitoring of their blood pressure throughout the study.
- Stable dietary habits and regimen of treatment for concomitant diseases for 1 month or more prior to the Screening Visit.
- Subject able and willing to undergo oral glucose tolerance test (OGTT).
Exclusion Criteria
Part 1 (Healthy Subjects) and Part 2 (Type 2 Diabetic Patients):
- A clinically significant history of previous allergy / sensitivity to any of the GMC-252 components, NAC or diflunisal.
- Inability to communicate well with the Investigator (i.e., language problem, poor mental development or impaired cerebral function).
- Participation in a New Chemical Entity clinical study within the previous 4 months or a marketed drug clinical study within the previous 3 months. (N.B. washout period between studies is defined as the period of time elapsed between the last dose of the previous study and the first dose of the next study).
- Donation of 450 mL or more blood within the previous 3 months.
- A clinically significant history of drug, alcohol or other substance abuse in the past 2 years.
Additional Criteria for Part 1 (Healthy Subjects):
- A clinically significant history of gastrointestinal disorder likely to influence drug absorption.
- Receipt of regular medication within 28days of the first dose that may have an impact on the safety and objectives of the study (at the Investigator's discretion).
- Evidence of renal, hepatic, central nervous system, respiratory, cardiovascular or metabolic dysfunction.
Additional Criteria for Part 2 (Type 2 Diabetic Patients):
Diagnosis/General Health:
- Diabetic autonomic or sensory neuropathy including gastroparesis, diabetic nephropathy or untreated active proliferative retinopathy.
- Clinically significant abnormalities in laboratory evaluation (including clinical biochemistry, haematology and urinalysis) in the opinion of the Investigator.
Diseases:
- Uncontrolled hypertension (blood pressure ≥ 160/100 mmHg), severe or unstable angina, coronary insufficiency, congestive heart failure, clinically significant (in the opinion of the Investigator) renal or hepatic disease.
- Previous gastric or intestinal surgerythat might impact drug absorption.
- Malignancy within 5 years of the start of the study, except for successfully treated local basal cell carcinoma
- Current or relevant previous history, of clinically significant psychiatric illness.
Medications:
- Current use of insulin or any previous use of insulin other than as part of a clinical trial or associated with surgical procedure or acute illness for up to 7 days.
- Use of any anti diabetic medication other than metformin in the 3 months prior to study entry.
- Current use of any anticoagulant drug e.g. warfarin, heparin.
- Prior use (within 48 h of dosing) of any drug that could have altered gastric motility (domperidone, cyclizine, metoclopramide, prochlorperazine), or cholestyramine.
Sites / Locations
- BioKinetic Europe Ltd.
- Simbec Research Ltd
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Placebo Comparator
Placebo Comparator
Placebo Comparator
Placebo Comparator
Cohort 1 (Part 1)
Cohort 2 (Part 1)
Cohort 3 (Part 1)
Cohort 4 (Part 2)
Multiple ascending oral administrations of GMC-252-L-Lysine Salt and matching placebo Interventions: Drug: GMC-252-L-Lysine Salt Other: Placebo
Multiple ascending oral administrations of GMC-252-L-Lysine Salt and matching placebo Interventions: Drug: GMC-252-L-Lysine Salt Other: Placebo
Multiple ascending oral administrations of GMC-252-L-Lysine Salt and matching placebo Interventions: Drug: GMC-252-L-Lysine Salt Other: Placebo
Multiple ascending oral administrations of GMC-252-L-Lysine Salt and matching placebo Interventions: Drug: GMC-252-L-Lysine Salt Other: Placebo