A randomized, double-blind, placebo-controlled single-ascending dose study to investigate safety, tolerability, pharmacokinetics and pharmacodynamics of subcutaneous PN-477 in obese or overweight adult participants
Overweight, obese
This is a randomized, double-blind, single-ascending dose study to assess the safety, tolerability, PK and PD of single ascending doses of PN-477. The study consists of 5 planned subcutaneous dosing cohorts comprising 8 participants per cohort. The starting dose will be multiple folds below the recommended maximum starting dose. Doses will then be increased, depending on safety, tolerability and drug exposure levels in subsequent cohorts. The planned doses may be adjusted in response to the data after a cohort-by-cohort review by the safety review committee. Up to 2 additional cohorts may be added if needed based on the data. Within each cohort, participants will be randomly assigned to receive PN-477 or matched placebo. The first 2 participants (sentinel participants) in each cohort will be randomized 1:1 to receive PN-477 or placebo on Day 1. These participants will be monitored for 48 hours and, after review of the safety data from both participants and approval by the study Investigator, the additional 6 participants will be randomized to study drug (n=5 PN-477; n=1 placebo). Randomisation: Participants will be assigned a unique randomization number and receive their treatment according to a paper randomization schedule that will be provided to the unblinded site pharmacist. Code break envelopes will also be provided to the sites.
1. Adults aged 18 to 65 years 2. Men and women who are overweight or obese (BMI between 25 and 40 kg/m²) with a stable body weight for at least 3 months 3. Generally healthy, with no major medical problems based on medical history, physical examination, heart tests, and blood tests 4. Normal or acceptable blood test results, including sugar levels, liver and kidney function, and cholesterol, as assessed by the study doctor 5. Not pregnant or breastfeeding, and willing to use reliable birth control during the study and for a period after the last dose 6. Willing and able to understand the study, sign the consent form, and attend all required study visits
1. Current or past serious medical conditions involving the heart, lungs, liver, kidneys, stomach, intestines, hormones, nervous system, mental health, blood, immune system, or skin 2. Cancer within the past 5 years, except for certain early, fully treated cancers 3. Recent surgery, serious infection, or fever 4. Abnormal blood pressure, heart rate, or heart rhythm test results 5. Severe allergies, serious drug reactions, or sensitivity to the study medicine or its ingredients 6. Use of recreational drugs, excessive alcohol intake, or heavy smoking or nicotine use 7. Recent large blood donation, significant blood loss, or blood transfusion 8. Recent participation in another clinical trial or recent use of an investigational drug or device 9. Inability or unwillingness to follow study instructions or considered unsuitable by the study doctor