A Drug-Drug Interaction (DDI) Study of HDM1002 With Repaglinide, Atorvastatin, Digoxin and Rosuvastatin in Healthy Subjects and Overweight Subjects.

A Phase I, Open-Label, Single-Arm, Fixed-Sequence Study to Evaluate the Effect of Repeated Administration of HDM1002 on the Pharmacokinetics of Repaglinide, Atorvastatin, Digoxin and Rosuvastatin in Healthy and Overweight Adult Chinese Subjects

The purpose of this study is to characterize the effect of HDM1002 on the PK of single dose of repaglinide, atorvastatin, digoxin and rosuvastatin in healthy adult subjects. The safety and tolerability of HDM1002 with repaglinide, atorvastatin, digoxin and rosuvastatin when given separately or together will also be evaluated.

Study Overview

• Status: Not yet recruiting
• Conditions: Healthy Adult Subject; Overweight Subject
• Intervention / Treatment: Drug: HDM1002; Drug: Repaglinide; Drug: Atorvastatin; Drug: Digoxin; Drug: Rosuvastatin

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Cheng Cui; Phone Number: +86-010 82266455; Email: cuicheng1226@163.com

Study Locations

• China
  • Beijing, China
    • Peking University Third Hospital
    • Principal Investigator: Dongyang Liu
    • Principal Investigator: Cui Cheng
    • Principal Investigator: Xiaohong Wang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. According to the medical history, clinical laboratory test results, vital sign measurements, 12 lead ECG results, and physical examination results during the screening period, the investigator considers the subject to be in good general health.
2. Age range of 18-45 years old (including range), no limit to gender.
3. Male subject weighed ≥50.0 kg, female subject weighed ≥45.0 kg, and a body mass index (BMI) within the range of 19.0 - 30.0 kg/m2 (including cut-off values).

Exclusion Criteria:

1. Subject has a history or family history of medullary thyroid cancer, thyroid C-cell hyperplasia, or multiple endocrine neoplasia type 2 (MEN2), or calcitonin≥50 ng/L during the screening period.
2. History of chronic pancreatitis or an episode of acute pancreatitis within 3 months prior to screening.
3. History of acute cholecystitis attack within 3 months prior to screening.
4. Subject judged by investigator has dysphagia, diseases or conditions that affect gastric emptying, or affect the absorption of gastrointestinal nutrients, such as bariatric surgery or other gastrectomy, irritable bowel syndrome, dyspepsia, etc.
5. History of previous surgery that will affect the absorption, distribution, metabolism, and excretion of drugs or plan to undergo surgery during the study period.
6. During screening period, any abnormalities in physical examination, electrocardiogram, laboratory tests, and vital signs which are of clinically significant .
7. Taken or planned to take any drug that effect liver enzyme or transporter activity within 28 days prior to taking the investigational drug.
8. History of clinically significant cardiovascular and cerebrovascular disease within 6 months prior to screening or at the time of admission.
9. Presence of clinically significant ECG results judged by the investigator at screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HDM1002 with Repaglinide, Atorvastatin, Digoxin and Rosuvastatin; Period 1: Single dose of repaglinide, atorvastatin, digoxin and rosuvastatin Period 2: Once daily dose of HDM1002 Period 3: Single dose of repaglinide, atorvastatin, digoxin and rosuvastatin with once daily dose of HDM1002	Drug: HDM1002; Administered orally; Drug: Repaglinide; Single dose; Administered orally; Drug: Atorvastatin; Single dose; Administered orally; Drug: Digoxin; Single dose; Administered orally; Drug: Rosuvastatin; Single dose; Administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC[0-∞]	Pharmacokinetics (PK) parameter of repaglinide, atorvastatin, digoxin and rosuvastatin: Area under the curve from time 0 hour to ∞	Period 1 and Period 3: Day 1-Day 16
AUC[0-t]	PK parameter of repaglinide, atorvastatin, digoxin and rosuvastatin: Area under the curve from time 0 to t hour	Period 1 and Period 3: Day 1-Day 16
Cmax	PK parameter of repaglinide, atorvastatin, digoxin and rosuvastatin: Maximum observed concentration	Period 1 and Period 3: Day 1-Day 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tmax	PK parameter of repaglinide, atorvastatin, digoxin and rosuvastatin: Time to maximum plasma concentration	Period 1 and Period 3: Day 1-Day 16
t1/2	PK parameter of repaglinide, atorvastatin, digoxin and rosuvastatin: Half life	Period 1 and Period 3: Day 1-Day 16
CL/F	PK parameter of repaglinide, atorvastatin, digoxin and rosuvastatin: Apparent Clearance	Period 1 and Period 3: Day 1-Day 16
Vz/F	PK parameter of repaglinide, atorvastatin, digoxin and rosuvastatin: Apparent volume of distribution	Period 1 and Period 3: Day 1-Day 16
Adverse events (AEs)	Number of subjects reporting AEs	Period 1 and Period 3: Day 1-Day 16, Period 2: Day 1-Day 35

Collaborators and Investigators

• Sponsor: Hangzhou Zhongmei Huadong Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2024
• Primary Completion (Estimated): February 1, 2025
• Study Completion (Estimated): April 1, 2025

Study Registration Dates

• First Submitted: September 3, 2024
• First Submitted That Met QC Criteria: September 14, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Actual): September 23, 2024
• Last Update Submitted That Met QC Criteria: September 19, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: Glucagon-Like Peptide-1 Receptor Agonists; HDM1002
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Body Weight; Overweight; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Enzyme Inhibitors; Antimetabolites; Protective Agents; Cardiotonic Agents; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Digoxin; Atorvastatin; Rosuvastatin Calcium; Repaglinide
• Other Study ID Numbers: HDM1002-106

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No