First-in-human Study of the Safety, Tolerability, Pharmacokinetics, and Food Effect of ACCG-2671

Phase 2RecruitingNCT07815678

Aconcagua Bio, Inc. a wholly owned subsidiary of Structure Therapeutics164 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

164

Conditions

Obesity

Interventions

ACCG-2671DRUG

Administered orally

PlaceboDRUG

Administered orally

Eligibility

Sex: ALLMin age: 25 YearsMax age: 75 YearsHealthy volunteers:

Medical Language ↔ Plain English

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 exclusion criteria at the Screening Visit or prior to first dose administration * History or presence of significant CV, pulmonary, hepatic, renal, hematological, GI, endocrine, immunologic, dermatologic, psychiatric, or neurological disease, including any acute illness or major surgery within the past 3 months, or any clinical laboratory abnormality determined by the Investigator to be clinically significant * Use of any prescription or over-the counter-medication including herbal products, diet aids, vitamins, or hormone supplements (including contraceptives) within 10 days or 5 times the apparent elimination half-life of the medication (whichever is longer) before the first study drug administration and throughout the study. Exceptions include injectable GLP-1RA treatment for Part 3, Cohort 2c only and medications used to manage AEs at the discretion of an investigator after consultation with the Sponsor.

Locations (6)

Research Site

Cypress, California, United States

NOT_YET_RECRUITING

Research Site

Lake Forest, California, United States

RECRUITING

Research Site

Decatur, Georgia, United States

Outcomes

Primary Outcomes

Number of participants with one or more adverse events (AEs) as assessed by CTCAE v5.0

Time frame: 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

Time frame: 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

Time frame: Baseline to Day 21 (Part 2)

Change from baseline in systolic blood pressure

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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)

Central Contacts

Sara Ahmed MD

CONTACT

650-647-0091 sara.ahmed@structuretx.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Research Site

Dilworth, Minnesota, United States

RECRUITING

Research Site

Springfield, Missouri, United States

NOT_YET_RECRUITING

Research Site

Webster, Texas, United States

RECRUITING

Change from baseline ECG QRS duration

Time frame: 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)

Time frame: 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

Time frame: 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

Time frame: 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)

Time frame: 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

Time frame: 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

Time frame: 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)

Time frame: 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)

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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)

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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)

Time frame: 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

Time frame: 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)

Time frame: 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)

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Change from baseline in urinalysis (Including pH, specific gravity, glucose, protein, ketones, blood, nitrites, urobilinogen, and leukocyte esterase)

Time frame: 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)

Secondary Outcomes

Maximum observed plasma concentration (Cmax) of ACCG-2671

Maximum observed plasma concentration of ACCG-2671

Time frame: Predose through Day 22 (Part 1); predose through Day 18 (Part 2); predose through Day 112 (Part 3)

Area under the plasma concentration-time curve from time zero to infinity (AUC0-inf) of ACCG-2671

Plasma AUC0-inf of ACCG-2671 following administration

Time frame: Predose through Day 22 (Part 1); predose through Day 18 (Part 2)

Area under the plasma concentration-time curve from time zero to the last quantifiable concentration (AUC0-t) of ACCG-2671

Plasma AUC0-t of ACCG-2671

Time frame: Predose through Day 22 (Part 1); predose through Day 18 (Part 2); predose through Day 112 (Part 3)

Area under the plasma concentration-time curve over a dosing interval (AUC0-tau) of ACCG-2671

Plasma AUC0-tau of ACCG-2671, where tau is the dosing interval

Time frame: Predose through Day 112 (Part 3)

Time to reach maximum observed plasma concentration (Tmax) of ACCG-2671

Time to reach the maximum observed plasma concentration of ACCG-2671

Time frame: Predose through Day 22 (Part 1); predose through Day 18 (Part 2); predose through Day 112 (Part 3)

Terminal elimination half-life (t½) of ACCG-2671

Terminal elimination half-life of ACCG-2671 in plasma

Time frame: Predose through Day 22 (Part 1); predose through Day 18 (Part 2); predose through Day 112 (Part 3)

Trough plasma concentration (Ctrough) of ACCG-2671

Predose plasma concentration of ACCG-2671 at the end of the dosing interval.

Time frame: Predose through Day 112 (Part 3)

Amount of ACCG-2671 excreted unchanged in urine (Ae)

Cumulative amount of ACCG-2671 excreted unchanged in urine

Time frame: Day -1 through Day 7 (Part 1, Cohorts 4 and 5)

Fraction of ACCG-2671 excreted unchanged in urine (Fe)

Fraction of the administered ACCG-2671 dose excreted unchanged in urine.

Time frame: Day -1 through Day 7 (Part 1, Cohorts 4 and 5)

Renal clearance (CLr) of ACCG-2671

Renal clearance of ACCG-2671

Time frame: Day -1 through Day 7 (Part 1, Cohorts 4 and 5)