A First-In-Human Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GUB014295

• Status: Recruiting
• Trial end date: 2024-12-01
• Target enrollment: 0
• Participant gender: Male

Summary

This is a single center, double-blind, randomized, placebo-controlled, single ascending subcutaneous dose study in lean to overweight or obese but otherwise healthy men. It is planned to enroll 4 cohorts of 8 subjects (Regimens A, B, C and D), with 2 additional optional cohorts of 8 subjects (Regimens E and F). Within each cohort, subjects will be randomized in a ratio of 6 active to 2 placebo. The primary objective is to assess the safety. Secondary objectives are to characterize the pharmacokinetics (PK) and to investigate pharmacodynamic effects.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Gubra A/S
• Collaborator: Quotient Sciences

Criteria

Inclusion Criteria:

• Lean to overweight or obese but otherwise healthy males

• BMI of 22.0 to 32.0 kg/m2 as measured at screening.

• Overweight or obese as assessed by BMI should be due to excess adipose tissue, as judged by the investigator

• Weight ≥70 kg at screening

Exclusion Criteria:

• Medical/Surgical History and Mental Health

• Serious adverse reaction or serious hypersensitivity to any drug or formulation excipients

• Presence or history of clinically significant allergy requiring treatment, as judged by the investigator.

• Hay fever is allowed unless it is active

• Known or suspected hypersensitivity or allergy to paracetamol

• Presence or history of clinically significant cardiovascular, renal, hepatic, dermatological, respiratory, neurological, psychiatric, malignant, metabolic, endocrinological, haematological or venereal disorder, as judged by the investigator

• Presence or history of any clinically relevant gastrointestinal diseases or symptoms of gastrointestinal disorders potentially affecting interpretation of study data.

• Presence or history of diseases associated with impaired calcium homeostasis and/or increased bone turnover (e.g. Paget´s disease, osteoporosis)

• History of major depressive disorder within 2 years prior to screening

• Subjects unable to take paracetamol for any reason

• Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator or delegate at screening

• Subjects with tattoos or scars on the abdomen which may interfere with injection site assessments as determined by the investigator or delegate at screening

• Clinically significant abnormal clinical chemistry, haematology, coagulation or urinalysis as judged by the investigator .

• Subjects with Gilbert's Syndrome are not allowed.

• HbA1c ≥48 mmol/mol (≥6.5%) and/or fasting plasma glucose ≥7.0 mmol/L at screening

• Prolongation of the QTcF over 450 msec or any other clinically significant abnormal ECG results as judged by the investigator

• Supine blood pressure (after ≥5 min rest) <90 mmHg or >150 mmHg (systolic) and/or <50 mmHg or >90 mmHg (diastolic)

• Heart rate (ECG-recorded after ≥5 min rest) <45 or >90 beats per minute

• Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) 1 and 2 antibody results

• Evidence of renal impairment at screening, as indicated by an estimated glomerular filtration rate (eGFR) of <80 mL/min/1.73m2

• Subjects who have received any investigational medicinal product (IMP) in a clinical research study within the 90 days prior to Day 1, or less than 5 elimination half-lives prior to Day 1, whichever is longer

• Subjects who have previously been administered IMP in this study

• Donation of blood or plasma within the previous 3 months or loss of greater than 400 mL of blood

• Subjects who are taking, or have taken, any prescribed or over-the-counter drug or herbal remedies/vitamins in the 14 days before IMP administration.

• Paracetamol (up to 4 g per day) will be permitted except in the 48 h prior to the mixed meal tests on Day -1 and Day 4 for Cohorts 2 to 6 where paracetamol is not permitted.

• NSAIDs can be given at the discretion of the investigator to treat any AEs if necessary;

• Subject reports prior receipt of an amylin and/or calcitonin receptor agonist within the last 6 months

• History of any drug or alcohol abuse in the past 2 years

• Regular alcohol consumption >21 units per week

• A confirmed positive alcohol breath test at screening or admission

• Current smokers and those who have smoked within the last 12 months

• Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months

• A confirmed breath carbon monoxide reading of greater than 10 ppm at screening or admission

• Confirmed positive drugs of abuse test result at screening or admission

• Anticipated change in lifestyle (such as eating, exercise or sleeping pattern) during the trial and/or clinically significant body weight change (≥5% self-reported change) or comprehensive dieting attempts (e.g. participation in a weight reduction program or treatment with any medication indicated for weight management) within the last 90 days prior to screening

• Subjects who do not agree to consume the liquid mixed meal

• Male subjects with pregnant or lactating partners

• Any disorder, unwillingness or inability, not covered by any of the other exclusion criteria, that the investigator evaluates might jeopardise the subject's safety or compliance with the protocol