Obesity
Conditions
Keywords
Obesity, Amylin, Structure Therapeutics, Intervention/Treatment, Drug: Placebo, DRUG:ACCG-2671
Brief summary
This first-in-human study will evaluate the safety, tolerability, and pharmacokinetics of single and multiple ascending oral doses of ACCG-2671. It will also evaluate the effect of food on the pharmacokinetics, safety, and tolerability of a single dose. Parts 1 and 2 will enroll healthy participants, and Part 3 will enroll otherwise healthy participants with obesity.
Detailed description
ACCG-2671 is a nonpeptide dual amylin and calcitonin receptor agonist (DACRA) This study comprises 3 parts: Part 1 (Single Ascending Dose \[SAD\]) will be conducted in healthy participants to assess the safety, tolerability, and PK profile of a single oral dose of ACCG-2671 or -matched placebo (SAD Cohorts 1 through 5). Part 2 (Food Effect) will be conducted in healthy participants to assess the effect of food intake on the PK, safety, and tolerability of a single oral dose of ACCG-2671 under fasted and fed conditions. Part 3 (Multiple Ascending Dose \[MAD\]) will be conducted in otherwise healthy, participants with obesity (BMI ≥ 30 kg/m2) to assess the safety, tolerability, PK profiles of ACCG-2671 or matched placebo administered for 84 days (MAD Cohorts 1 through 5) Safety Review Committee (SRC) meetings will be held prior to dose escalation for Part 1 (SAD) and Part 3 (MAD) cohorts in the study. The decisions on dose escalation will be based on safety and laboratory data and available PK data from each cohort.
Interventions
DRUGACCG-2671
Administered orally
DRUGPlacebo
Administered orally
Sponsors
Aconcagua Bio, Inc. a wholly owned subsidiary of Structure Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
25 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Signed informed consent * Men and women with the following at the time of Screening for Part 1 and 2: ≥25 years and ≤65 years of age and BMI ≥18.0 kg/m2 and \<30.0 kg/m2 * For Part 3, ≥25 years and ≤75 years of age and BMI ≥30.0 kg/m2 * For Part 3, receiving a stable dose of an injectable GLP-1RA for ≥3 months, who responded to GLP1RA treatment with stable body weight and no ongoing GLP-1RA-related symptoms or AEs. For the duration of the study, participants must not be planning to change GLP-1RA dose or discontinue GLP-1RA treatment * Body weight ≥50.0 kg at time of screening
Exclusion criteria
* For Parts 1 and Part 2: Participants with any clinically significant medical conditions are excluded from the study. * For Parts 1, 2 and 3: participants will be excluded from this study if there is evidence of ANY of the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with one or more adverse events (AEs) as assessed by CTCAE v5.0 | Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 24 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3) | — |
| Number of participants with one or more serious adverse advents (SAEs) as assessed by CTCAE v5.0 | Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 24 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3) | — |
| Number of participants with one or more treatment-emergent adverse events (TEAEs) as assessed by CTCAE v5.0 | Baseline to Day 21 (Part 2) | — |
| Change from baseline in systolic blood pressure | Baseline to Day 15 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3) | — |
| Change from baseline in diastolic blood pressure | Baseline to Day 15 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3) | — |
| Change from baseline in heart rate | Baseline to Day 15 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3) | — |
| Change from baseline in ECG ventricular heart rate | Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); predose to Day 70 (Part 3) | — |
| Change from baseline in ECG PR interval | Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); predose to Day 70 (Part 3) | — |
| Change from baseline ECG QRS duration | Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); predose to Day 70 (Part 3) | — |
| Change from baseline in ECG QT Interval corrected using Fridericia's Formula (QTcF) | Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); predose to Day 70 (Part 3) | — |
| Change from baseline in hemoglobin | Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3) | — |
| Change from baseline in hematocrit | Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3) | — |
| Change from baseline in thrombocyte count (platelet count) | Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3) | — |
| Change from baseline in white blood cell (WBC) count | Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3) | — |
| Change from baseline in prothrombin time | Baseline to day 17 (Part 1, Cohorts 1, 2, and 3); baseline to day 22 (Part 1, Cohorts 4 and 5); baseline to day 21 (Part 2); baseline to day 112 (Part 3) | — |
| Change from baseline in international normalized ratio (INR) | Baseline to day 17 (Part 1, Cohorts 1, 2 and 3); baseline to day 22 (Part 1 Cohorts 4 and 5); baseline to day 21 (Part 2); baseline to day 112 (Part 3) | — |
| Change from baseline in activated partial thromboplastin time (aPTT) | Baseline to day 17 (Part 1, Cohorts 1, 2 and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3) | — |
| Change from baseline in fibrinogen activity | Baseline to Day 17 (Part 1, Cohorts 1, 2 and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3) | — |
| Change from baseline in sodium | Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3) | — |
| Change from baseline in potassium | Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3) | — |
| Change from baseline in chloride | Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3) | — |
| Change from baseline in phosphate | Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3) | — |
| Change from baseline in calcium | Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3) | — |
| Change from baseline in glucose | Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3) | — |
| Change from baseline in amylase | Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3) | — |
| Change from baseline in lipase | Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3) | — |
| Change from baseline in magnesium | Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3) | — |
| Change from baseline in albumin | Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3) | — |
| Change from baseline in lactate dehydrogenase (LDH) | Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3) | — |
| Change from baseline in creatine kinase | Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3) | — |
| Change from baseline in creatinine | Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3) | — |
| Change from baseline in blood urea nitrogen | Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3) | — |
| Change from baseline in alanine aminotransferase (ALT) | Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3) | — |
| Change from baseline in total alkaline phosphatase | Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3) | — |
| Change from baseline in aspartate aminotransferase (AST) | Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3) | — |
| Change from baseline in gamma-glutamyl transferase (GGT) | Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3) | — |
| Change from baseline in total bilirubin | Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3) | — |
| Change from baseline in direct bilirubin | Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3) | — |
| Change from baseline in indirect bilirubin | Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3) | — |
| Number of participants with abnormal urinalysis parameters | Baseline to Day 17 (Part 1, Cohorts 1, 2, and 3); baseline to Day 22 (Part 1, Cohorts 4 and 5); baseline to Day 21 (Part 2); baseline to Day 112 (Part 3) | Change from baseline in urinalysis (Including pH, specific gravity, glucose, protein, ketones, blood, nitrites, urobilinogen, and leukocyte esterase) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum observed plasma concentration (Cmax) of ACCG-2671 | Predose through Day 22 (Part 1); predose through Day 18 (Part 2); predose through Day 112 (Part 3) | Maximum observed plasma concentration of ACCG-2671 |
| Area under the plasma concentration-time curve from time zero to infinity (AUC0-inf) of ACCG-2671 | Predose through Day 22 (Part 1); predose through Day 18 (Part 2) | Plasma AUC0-inf of ACCG-2671 following administration |
| Area under the plasma concentration-time curve from time zero to the last quantifiable concentration (AUC0-t) of ACCG-2671 | Predose through Day 22 (Part 1); predose through Day 18 (Part 2); predose through Day 112 (Part 3) | Plasma AUC0-t of ACCG-2671 |
| Area under the plasma concentration-time curve over a dosing interval (AUC0-tau) of ACCG-2671 | Predose through Day 112 (Part 3) | Plasma AUC0-tau of ACCG-2671, where tau is the dosing interval |
| Time to reach maximum observed plasma concentration (Tmax) of ACCG-2671 | Predose through Day 22 (Part 1); predose through Day 18 (Part 2); predose through Day 112 (Part 3) | Time to reach the maximum observed plasma concentration of ACCG-2671 |
| Terminal elimination half-life (t½) of ACCG-2671 | Predose through Day 22 (Part 1); predose through Day 18 (Part 2); predose through Day 112 (Part 3) | Terminal elimination half-life of ACCG-2671 in plasma |
| Trough plasma concentration (Ctrough) of ACCG-2671 | Predose through Day 112 (Part 3) | Predose plasma concentration of ACCG-2671 at the end of the dosing interval. |
| Amount of ACCG-2671 excreted unchanged in urine (Ae) | Day -1 through Day 7 (Part 1, Cohorts 4 and 5) | Cumulative amount of ACCG-2671 excreted unchanged in urine |
| Fraction of ACCG-2671 excreted unchanged in urine (Fe) | Day -1 through Day 7 (Part 1, Cohorts 4 and 5) | Fraction of the administered ACCG-2671 dose excreted unchanged in urine. |
| Renal clearance (CLr) of ACCG-2671 | Day -1 through Day 7 (Part 1, Cohorts 4 and 5) | Renal clearance of ACCG-2671 |
Countries
United States
Contacts
CONTACTSara Ahmed MD
Outcome results
None listed