A Two-Part First-In-Human Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GUB014295
- Conditions
- Healthy VolunteersOverweight
- Registration Number
- NCT06144684
- Lead Sponsor
- Gubra A/S
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 100
Inclusion Criteria:<br><br> - Males (Part 1 and 2) and females (Part 2 only) aged 18 to 55 years inclusive at the<br> time of signing informed consent<br><br> - Lean to overweight or obese but otherwise healthy males (Part 1 and 2) or<br> non-pregnant, non-lactating females of non-childbearing potential (Part 2 only)<br><br> - BMI of 22.0 to 32.0 kg/m2 for Part 1 and Part 2A, and a BMI of 27.0 to 35.0 kg/m2<br> for Part 2B, as measured at screening.<br><br> - Overweight or obese as assessed by BMI should be due to excess adipose tissue, as<br> judged by the investigator<br><br> - Weight =70 kg (all parts) and =110 kg (Part 2A and 2B only) at screeningBMI of 22.0<br> to 32.0 kg/m2 as measured at screening.<br><br>Exclusion Criteria:<br><br> - Serious adverse reaction or serious hypersensitivity to any drug or formulation<br> excipients<br><br> - Presence or history of clinically significant allergy requiring treatment, as judged<br> by the investigator. Hay fever is allowed unless it is active<br><br> - Known or suspected hypersensitivity or allergy to paracetamol<br><br> - Presence or history of clinically significant cardiovascular, renal, hepatic,<br> dermatological, respiratory, neurological, psychiatric, malignant, metabolic,<br> endocrinological, haematological or venereal disorder, as judged by the investigator<br><br> - Presence or history of any clinically relevant gastrointestinal diseases or symptoms<br> of gastrointestinal disorders potentially affecting interpretation of study data.<br><br> - Presence or history of diseases associated with impaired calcium homeostasis and/or<br> increased bone turnover (e.g. Paget´s disease, osteoporosis)<br><br> - History of major depressive disorder within 2 years prior to screening<br><br> - Subjects unable to take paracetamol for any reason<br><br> - Subjects who do not have suitable veins for multiple venepunctures/cannulation as<br> assessed by the investigator or delegate at screening<br><br> - Subjects with tattoos or scars on the abdomen which may interfere with injection<br> site assessments as determined by the investigator or delegate at screening<br><br> - Clinically significant abnormal clinical chemistry, haematology, coagulation or<br> urinalysis as judged by the investigator. Subjects with Gilbert's Syndrome are not<br> allowed.<br><br> - HbA1c =48 mmol/mol (=6.5%) and/or fasting plasma glucose =7.0 mmol/L at screening<br><br> - Part 2B only: Subjects with haemoglobin <LLN at screening and/or admission<br><br> - Prolongation of the QTcF over 450 msec or any other clinically significant abnormal<br> ECG results as judged by the investigator<br><br> - Supine blood pressure (after =5 min rest) <90 mmHg or >150 mmHg (systolic) and/or<br> <50 mmHg or >90 mmHg (diastolic)<br><br> - Heart rate (ECG-recorded after =5 min rest) <45 or >90 beats per minute<br><br> - Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or<br> human immunodeficiency virus (HIV) 1 and 2 antibody results<br><br> - Evidence of renal impairment at screening, as indicated by an estimated glomerular<br> filtration rate (eGFR) of <80 mL/min/1.73m2<br><br> - Part 2A and 2B only: Females of childbearing potential including those who are<br> pregnant or lactating (all female subjects must have a negative highly sensitive<br> urine or serum pregnancy test)<br><br> - Subjects who have received any investigational medicinal product (IMP) in a clinical<br> research study within the 90 days prior to Day 1, or less than 5 elimination<br> half-lives prior to Day 1, whichever is longer<br><br> - Subjects who have previously been administered IMP in this study<br><br> - Donation of blood or plasma within the previous 3 months or loss of greater than 400<br> mL of blood<br><br> - Subjects who are taking, or have taken, any prescribed or over-the-counter drug or<br> herbal remedies/vitamins in the 14 days before IMP administration.<br><br> - Paracetamol (up to 4 g per day) will be permitted except in the 48 h prior to the<br> mixed meal tests on Day -1 and Day 4 (Part 1 Cohorts 2 to 6), Day 39 (Part 2A) and<br> Day 81 (Part 2B) where paracetamol is not permitted.<br><br> - NSAIDs can be given at the discretion of the investigator to treat any AEs if<br> necessary;<br><br> - Subject reports prior receipt of an amylin and/or calcitonin receptor agonist within<br> the last 6 months<br><br> - History of any drug or alcohol abuse in the past 2 years<br><br> - Regular alcohol consumption >21 units per week<br><br> - A confirmed positive alcohol breath test at screening or admission<br><br> - Current smokers and those who have smoked within the last 12 months<br><br> - Current users of e-cigarettes and nicotine replacement products and those who have<br> used these products within the last 12 months<br><br> - A confirmed breath carbon monoxide reading of greater than 10 ppm at screening or<br> admission<br><br> - Confirmed positive drugs of abuse test result at screening or admission<br><br> - Anticipated change in lifestyle (such as eating, exercise or sleeping pattern)<br> during the trial and/or clinically significant body weight change (=5% self-reported<br> change) or comprehensive dieting attempts (e.g. participation in a weight reduction<br> program or treatment with any medication indicated for weight management) within the<br> last 90 days prior to screening<br><br> - Subjects who do not agree to consume the liquid mixed meal<br><br> - Male subjects with pregnant or lactating partners<br><br> - Any disorder, unwillingness or inability, not covered by any of the other exclusion<br> criteria, that the investigator evaluates might jeopardise the subject's safety or<br> compliance with the protocol
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Safety - Adverse Events (AE) incidence;Safety - changes in vital signs;Safety - Safety laboratory parameters
- Secondary Outcome Measures
Name Time Method Pharmacokinetic (PK) - Tmax and Cmax;Pharmacokinetic (PK) - area under the concentration curve (AUC);Pharmacokinetic (PK) - T1/2;Pharmacokinetic (PK) - CL/F;Pharmacokinetic (PK) - Vz/F