Multiple Ascending Dose Study of GMC-252-L-Lys Salt in Healthy Subjects and Type 2 Diabetics

NCT02744820 | Terminated Phase 1

• 1 other identifier: GMC-252-1.03
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to assess the safety, tolerability and pharmacokinetics (PK) of multiple oral doses of GMC-252-L-Lysine salt (GMC-252) in healthy subjects and type 2 diabetics. The secondary objective is to explore the effect of multiple oral doses of GMC-252 on pharmacodynamic(PD) parameters in type 2 diabetics.

Conditions

Healthy; Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• Number of Participants with Serious and Non-Serious Adverse Events

  Physical status (Vital signs; 12-lead ECG; Urinalysis; Haematology and biochemistry)

  28 days plus 14 days post last dose

Secondary Outcomes (3)

• Maximal Concentration (Cmax)

  28 days plus 14 days post last dose

• Area Under the Concentration-Time Curve

  28 days plus 14 days post last dose

• Time to reach steady state

  28 days plus 14 days post last dose

Other Outcomes (6)

• Preliminary effect on Fasting blood glucose (Cohort 4 only)

  28 days plus 14 days post last dose

• Preliminary effect on oral glucose tolerance test (OGTT) (Cohort 4 only)

  28 days plus 14 days post last dose

• Preliminary effect on Insulin levels (Cohort 4 only)

  28 days plus 14 days post last dose

Study Arms (4)

Cohort 1 (Part 1)

PLACEBO COMPARATOR

Multiple ascending oral administrations of GMC-252-L-Lysine Salt and matching placebo Interventions: Drug: GMC-252-L-Lysine Salt Other: Placebo

Drug: GMC-252-L-Lysine Salt; Other: Placebo

Cohort 2 (Part 1)

PLACEBO COMPARATOR

Multiple ascending oral administrations of GMC-252-L-Lysine Salt and matching placebo Interventions: Drug: GMC-252-L-Lysine Salt Other: Placebo

Drug: GMC-252-L-Lysine Salt; Other: Placebo

Cohort 3 (Part 1)

PLACEBO COMPARATOR

Multiple ascending oral administrations of GMC-252-L-Lysine Salt and matching placebo Interventions: Drug: GMC-252-L-Lysine Salt Other: Placebo

Drug: GMC-252-L-Lysine Salt; Other: Placebo

Cohort 4 (Part 2)

PLACEBO COMPARATOR

Multiple ascending oral administrations of GMC-252-L-Lysine Salt and matching placebo Interventions: Drug: GMC-252-L-Lysine Salt Other: Placebo

Drug: GMC-252-L-Lysine Salt; Other: Placebo

Interventions

GMC-252-L-Lysine Salt DRUG

1 dose by oral route, once a day, 28 days

Also known as: GMC-252-L-Lys Salt

Cohort 1 (Part 1); Cohort 2 (Part 1); Cohort 3 (Part 1); Cohort 4 (Part 2)

Placebo OTHER

Matching doses by oral route, once a day, 28 days

Cohort 1 (Part 1); Cohort 2 (Part 1); Cohort 3 (Part 1); Cohort 4 (Part 2)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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:

Sponsors & Collaborators

• Genmedica Therapeutics S.L.: lead
• Simbec Research: collaborator

Study Sites (2)

BioKinetic Europe Ltd.

Belfast, BT2 7BA, United Kingdom

Location

Simbec Research Ltd

Merthyr Tydfil, CF48 4DR, United Kingdom

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Robert Adams, MBBS

  Simbec Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 13, 2016
• First Posted: April 20, 2016
• Study Start: April 1, 2016
• Primary Completion: September 1, 2017
• Study Completion: September 1, 2017
• Last Updated: October 12, 2017

Record last verified: 2017-10

Locations

GB (2)