None listed
Conditions
Brief summary
This is an open-label, formulation bridging and food-effect study which will compare 2 formulations in 3 separate crossover steps, as well as the effect of food (low-fat vs. high-fat diet). Who is it for? You may be eligible for this study if you are aged 18 to 65 years living with overweight or obesity, have a with a body mass index of greater than or equal to 27kg and less than 45kg without clinically significant (CS) medical history. Study details The aim of this study will be to assess the relative bioavailability of 2 formulations of aleniglipron in overweight or obese participants.
Interventions
The dosing range of aleniglipron will be from 5mg to 180mg by weekly dose escalation. Participants will receive one oral dose daily with no washout between treatments.
Starting on Day 1, dose titration of aleniglipron up to 180 mg will commence. Titration will consist of 5 mg QD on Days 1 to 5, followed by 15 mg QD on Days 6 to 10.
On Day 11, participants will be randomised in a 1:1 ratio to receive 45 mg QD for 3 days in a 2-way crossover fashion to assess formulation bridging under fasting c
The dosing range of aleniglipron will be from 5mg to 180mg by weekly dose escalation. Participants will receive one oral dose daily with no washout between treatments. Starting on Day 1, dose titration of aleniglipron up to 180 mg will commence. Titration will consist of 5 mg QD on Days 1 to 5, followed by 15 mg QD on Days 6 to 10. On Day 11, participants will be randomised in a 1:1 ratio to receive 45 mg QD for 3 days in a 2-way crossover fashion to assess formulation bridging under fasting conditions. On Day 17, participants will be randomised in a 1:1 ratio to receive 90 mg QD for 3 days in a 2-way crossover fashion to assess formulation bridging under fasting conditions. On Day 23, participants will be randomised in a 1:1 ratio to receive 180 mg QD for 3 days in a 2-way crossover fashion to assess formulation bridging under fasting conditions. Food effect assessment: On Day 31 and Day 34, participants will take the aleniglipron dose with either a low-fat or high-fat breakfast in a crossover fashion (each participant receives one breakfast type on Day 31 and the other on Day 34). Participants may take part in multiple crossover periods, including crossover assessments of different study treatment conditions for formulation evaluation and a separate crossover assessment under low-fat and high-fat meal conditions for food-effect evaluation. A low-fat breakfast will be (~400 to 500 calories and ~25% fat) AND A high-fat breakfast will be (~800 calories and ~50% fat). Participants will be dosed as in-patients and treatment adherence will be monitored by site staff.
Sponsors
Gasherbrum Bio, Inc.
Study design
Allocation
Randomised controlled trial
Intervention model
Other
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Participants must fulfill all of the following inclusion criteria to be eligible for participation in the study: 1.Adult males and females, 18 to 65 years of age (inclusive), at the screening visit. 2. Have body mass index (BMI) greater than or equal to 27.0 kg/m² and less than 45 kg/m2, at the screening visit. 3. Continuous nonsmoker who has not used nicotine or tobacco containing products for at least 3 months prior to the first dosing, based on participant self-reporting. 4.Female and male participants must follow protocol-specified contraception guidance. Male participants must agree not to donate sperm and, if engaging in sexual intercourse with a female partner who could become pregnant, must agree to use a highly effective method of contraception until greater than or equal to 90 days after the last dose of study drug 5. No clinically significant medical history, physical examination, clinical laboratory profiles, vital signs, or electrocardiograms (ECGs), as deemed by the Investigator or designee, including the following: • Seated blood pressure is greater than or equal to 90/40 mmHg and less than or equal to 150/90 mmHg at the screening visit; the measurement will be performed in triplicate and the average of all 3 measurements used to determine eligibility. • Seated heart rate is greater than or equal to 40 bpm and less than or equal to 99 bpm at the screening visit; if out of range, the measurements may be repeated 2 more times and the average of all 3 measurements used to determine eligibility. • QTcF interval is less than or equal to 450 msec (males) and less than or equal to 470 msec (females) and has ECG findings considered normal or not clinically significant by the Investigator or designee at the screening visit. • Amylase or lipase less than or equal to upper limit of normal (ULN) at the screening visit. • Estimated glomerular filtration rate greater than or equal to 60 mL/min at the screening visit or serum creatinine less than or equal to 1.1-fold above the ULN. 6. Have suitable venous access for blood sampling. 7. Willing and able to comply with all study assessments and adhere to the protocol schedule and restrictions. 8. Able to swallow multiple tablets. 9. Signed Informed Consent Form (ICF) before any study-related activities are initiated, understand the study procedures in the ICF, and be willing and able to comply with the protocol schedule and restrictions
Exclusion criteria
Participants must not be enrolled in the study if they meet any of the following criteria: 10. Previous documented diagnosis of diabetes mellitus (except for gestational diabetes and the participant has a hemoglobin A1c less than 6.5%). 11. Is mentally or legally incapacitated at the time of the screening visit or expected during the conduct of the study. 12. History of a clinically significant medical or psychiatric condition (e.g., schizophrenia, bipolar disorder, or other serious mood or anxiety disorder) or disease in the opinion of the Investigator or designee within the last 2 years. 13. History of any illness that, in the opinion of the Investigator or designee, might confound the results of the study or pose an additional risk to the participant by their participation in the study. 14. History of chronic pancreatitis or idiopathic acute pancreatitis, or documented history of biliary stones. A participant with a history of acute pancreatitis caused by gallstones may be included in the study if the participant has had a cholecystectomy greater than or equal to 90 days to resolve the problem. 15. Any other condition or prior therapy that in the opinion of the Investigator would make the participant unsuitable for this study, including inability to cooperate fully with the requirements of the study protocol or likelihood of noncompliance with any study requirements. 16. History or presence of alcohol or drug abuse (including participants with symptoms of cannabis disorder) within the past 2 years prior to the first dosing. 17. History or presence of hypersensitivity or idiosyncratic reaction to any of the study drugs or related compounds. 18. Consumption of grapefruit, tangelo, or Seville orange (or products containing grapefruit, tangelo, Seville orange, or other citrus products known to contain bergamottin) within 14 days before the first administration of study drug and throughout the study. 19. Any history of malignant disease in the last 5 years (excludes basal cell carcinoma or cervical carcinoma in situ). 20. History of ileus. 21. Chronic malabsorption, regardless of etiology. 22. History or presence of a documented diagnosis of cirrhosis. 23. History of Crohn’s disease, ulcerative colitis, or other inflammatory bowel disease or any other GI disease that would impede drug absorption. 24. At the screening visit, documented diagnosis of heart failure according to the New York Heart Association Class I, II, III, or IV. 25. Within the past year before the screening visit, any of the following: episode of acute coronary event, transient ischemic attack, stroke, peripheral arterial vascular disease leading to revascularization, or other significant cardiovascular event as determined by the Investigator. 26. Evidence of prolonged QRS interval greater than 120 msec; or risk factors for torsade de pointes (including a family history of long QT syndrome or sudden cardiac death). 27. Liver function test results elevated greater than 1.5 × above the ULN for aspartate transaminase (AST) or alanine transaminase (ALT), greater than 1.5 × ULN for bilirubin (total, conjugated, or unconjugated) or 3.0 × ULN for participants with known Gilbert’s Syndrome, or alkaline phosphatase (ALP) greater than 1.5 × ULN. 28.Female participant with a positive pregnancy test at the screening visit or at check-in, or who is lactating. 29. Positive test results for an active viral infection, such as: severe acute respiratory syndrome coronavirus 2; human immunodeficiency virus (HIV)-1 or HIV-2 with positive antibodies; hepatitis B infection, defined as positive hepatitis B core antibody and positive hepatitis B virus DNA, or positive hepatitis B surface antigen; or hepatitis C infection defined as positive hepatitis C antibody and positive hepatitis C RNA at the screening visit. 30. Any vaccinations within 14 days before the first dosing. 31. Serum calcitonin greater than ULN, a personal or family history of medullary thyroid carcinoma, or multiple endocrine neoplasia syndrome type 2 at the screening visit. 32. Have a fasting serum triglyceride level of greater than 500 mg/dL at the screening visit. 33. Positive urine drug or alcohol results at the screening visit or check-in. 34. Unable to abstain from using recreational drugs throughout the study. Participants who are in a drug recovery program that prescribes either methadone, buprenorphine/naloxone (Suboxone), or pentazocine (Talwin) will not be enrolled. 35. Use of strong CYP3A4 inducers or moderate to strong CYP3A4 inhibitors, drugs that are sensitive P-gp or BCRP substrates, or drugs that are P-gp inducers or P-gp inhibitors. Concomitant medications that are sensitive CYP3A4 substrates may require monitoring with or without dose reductions, according to the individual respective product labeling, as summarized. Concomitant use of lovastatin and simvastatin is not allowed; however, use of other statins is not prohibited. 36. Comply with the restrictions for diet. 37. Demonstrated clinically significant allergic reactions (e.g., food, drug, or atopic reactions, or asthmatic episodes) that required intervention, (e.g., emergency room visit or epinephrine administration) and which, in the opinion of the Investigator, would interfere with the participant’s ability to participate in the study. 38. History of chronic constipation, in the opinion of the Investigator, or complaints of abnormal bowel movement frequency within one month prior to the screening visit. 39. History of major depressive disorder within the last 2 years. 40. Have any history of suicide attempt or hospitalization for a psychiatric condition. 41. Patient Healthy Questionnaire-9 (PHQ-9) score greater than or equal to 15 at the screening visit and check-in. 42. On the Columbia-Suicide Severity Rating Scale (C-SSRS) – (the first assessment of C-SSRS will be the Baseline/Screening version; at all other time points, the Since Last Visit version will be administered): • A “yes” answer to Question 4 or Question 5 on the “Suicidal Ideation” portion of the C-SSRS or • A “yes” answer to any of the suicide-related behaviors (actual attempt, interrupted attempt, aborted attempt, preparatory act, or behavior) on the “Suicidal Behavior” portion of the C-SSRS 43. Donation of blood or significant blood loss (greater than 500 mL) within 56 days prior to first dosing. 44. Plasma donation within 7 days prior to first dosing. 45. Has been on a diet incompatible with the on-study diet, in the opinion of the Investigator or designee, within 30 days prior to the first dosing. 46. Participation in another clinical study within 30 days or within 5 half-lives (if known), prior to the first dosing, whichever is longer. The 30-day window will be derived from the date of the last blood collection or dosing, whichever is later, in the previous study to Day 1 of the current study. 47. Is lactose intolerant. 48. Use of medications intended to promote weight loss, within 6 months prior to the screening visit, 49. Are receiving metformin for any indication or have received metformin within 90 days prior to the screening visit.
Outcome results
None listed