Influence of JY09 on Pharmacokinetics of Metformin , Rosuvastatin , and Digoxin and the QT Interval Study in Overweight Chinese Subjects

NCT06247748 | Completed Phase 1

• 1 other identifier: dfbt-jy09-ow-2023-101
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

This trial is conducted in china. The aim of the trial is as follows:

• To assess the effect of multiple subcutaneous injections of JY09 injection on the pharmacokinetic (PK) profile of multiple oral doses of metformin hydrochloride tablets, a single oral dose of Rosuvastatin calcium tablets, or digoxin tablets in overweight Chinese subjects;
• To assess the effect of multiple subcutaneous injections of JY09 injection on QT interval in overweight Chinese subjects.

Conditions

Diabetes Mellitus, Type 2; Overweight

Keywords

JY09; QT Interval

Outcome Measures

Primary Outcomes (6)

• The Metformin Peak Concentration (Cmax )

  The peak concentration(Cmax） is the highest level of plasma concentration that occurs after administration.This parameter is an important index to reflect the absorption rate and degree of drug in vivo.

  During a dosing interval (0-36 hours) after the last of 7 repeated doses of metformin without JY09 exposure (Day 4) and at JY09 steady state (Day 88)

• Area under the Metformin blood concentration-time curve

  AUC refers to the area under the drug time curve, which is the area surrounded by the pharmacokinetic blood concentration curve to the time axis. This parameter is an important index to evaluate the degree of drug absorption, reflecting the exposure characteristics of drugs in vivo.

  During a dosing interval (0-36 hours) after the last of 7 repeated doses of metformin without JY09 exposure (Day 4) and at JY09 steady state (Day 88)

• The Rosuvastatin Peak Concentration (Cmax )

  The peak concentration(Cmax） is the highest level of plasma concentration that occurs after administration.This parameter is an important index to reflect the absorption rate and degree of drug in vivo.

  From time 0 to 96 hours after a single dose of Rosuvastatin without JY09 exposure (Day 8) and at JY09 steady state (Day 95)

• Area under the Rosuvastatin blood concentration-time curve

  Area under curve(AUC) refers to the area under the drug time curve, which is the area surrounded by the pharmacokinetic blood concentration curve to the time axis. This parameter is an important index to evaluate the degree of drug absorption, reflecting the exposure characteristics of drugs in vivo.

  From time 0 to 96 hours after a single dose of Rosuvastatin without JY09 exposure (Day 8) and at JY09 steady state (Day 95)

• The Digoxin Peak Concentration (Cmax )

  The peak concentration(Cmax） is the highest level of plasma concentration that occurs after administration.This parameter is an important index to reflect the absorption rate and degree of drug in vivo.

  From time 0 to 168 hours after a single dose of Digoxin without JY09 exposure (Day 15) and at JY09 steady state (Day 102)

• Baseline-corrected difference of Corrected QT interval after multiple subcutaneous injections of JY09 injection

  Corrected QT interval is a QT interval adjusted by heart rate, which is an index of cardiac depolarization and repolarization

  From time 0 to 72 hours after a single dose of JY09 (Day 22) and at JY09 steady state (Day 92)

Secondary Outcomes (11)

• Safety endpoint-Adverse events

  From baseline (Day -1) to follow-up (Day 123)

• Vital signs-Blood pressure

  From baseline (Day -1) to follow-up (Day 123)

• Vital signs-Pulse

  From baseline (Day -1) to follow-up (Day 123)

• Vital signs-Respiration

  From baseline (Day -1) to follow-up (Day 123)

• Physical examination

  From baseline (Day -1) to follow-up (Day 123)

Other Outcomes (16)

• Area Under the Effect Curve from time 0 to the last measurable concentration (AUEC0-t )

  From time 0 to 240 minutes after Oral glucose(Day21) and Oral glucose(Day84).

• The Peak Effect Concentration(ECmax）

  From time 0 to 240 minutes after Oral glucose(Day21) and Oral glucose(Day84).

• Maximum Effect Time(ETmax )

  From time 0 to 240 minutes after Oral glucose(Day21) and Oral glucose(Day84).

Study Arms (1)

Exendin-4 Fc fusion protein (JY09) injection

EXPERIMENTAL

D22 received a single subcutaneous abdominal injection of 1.2 mg of JY09 injection after completion of PK blood sampling; D29 to D78 received continuous subcutaneous abdominal injections of 2.4 mg of JY09 injection in the morning, once weekly (total of 8 administrations). All doses were to be administered within 3 min.

Drug: Exendin-4 Fc fusion protein (JY09) injection; Drug: Metformin Hydrochloride tablet; Drug: Rosuvastatin calcium tablets; Drug: Digoxin tablet

Interventions

Exendin-4 Fc fusion protein (JY09) injection DRUG

D22 received a single subcutaneous abdominal injection of 1.2 mg of JY09 injection after completion of PK blood sampling; D29, D36, D43, D50, D57, D64, D71, and D78 subjects returned to the study center to receive a subcutaneous abdominal injection of 2.4 mg of JY09 injection(total of 8 administrations).All doses were to be administered within 3 min.

Also known as: JY09

Exendin-4 Fc fusion protein (JY09) injection

Metformin Hydrochloride tablet DRUG

D1 to D4 continuous oral administration of 0.5 g metformin hydrochloride tablets twice daily (D4 was administered only in the morning, with a total of 7 administrations) for a washout period of 96 h;0.5 g metformin hydrochloride tablets orally twice a day continuously from D85 to D88 (D88 was given only in the morning, for a total of 7 doses).

Also known as: Metformin

Exendin-4 Fc fusion protein (JY09) injection

Rosuvastatin calcium tablets DRUG

D8 received a single oral administration of 10 mg of Rosuvastatin calcium tablets in the morning, with a washout period of 168 h,and 10 mg Rosuvastatin calcium tablets orally at 72 h ± 0.5 h (D95) after JY09 administration.

Also known as: Rosuvastatin

Exendin-4 Fc fusion protein (JY09) injection

Digoxin tablet DRUG

D15 received a single oral administration of 0.25 mg digoxin tablets in the morning, with a washout period of 168 h,oral 0.25 mg digoxin tablets 72 h±0.5 h after JY09 administration (D102)

Also known as: digoxin

Exendin-4 Fc fusion protein (JY09) injection

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age: Overweight subjects with full capacity for civil behavior who are ≥ 18 years old and ≤ 45 years old (the ratio of the number of subjects of either sex is not less than 1/3).
• Body weight: men ≥ 50.0 kg, women ≥ 45.0 kg, body mass index (BMI) ≥ 24.0 kg/m2 and ≤ 28.0 kg/m2 , BMI = weight (kg)/height (m2 ).
• Those who do not plan to have children in the last 6 months, do not plan to donate sperm/eggs, and are willing to use effective contraception for 6 months after the end of dosing.
• Fully understand the trial and possible adverse effects, have the ability to communicate normally with the investigator, as well as comply with study requirements, follow protocol procedures and limitations, and be able to visit on time.
• Understand the content of the informed consent form, agree to participate in this trial and voluntarily sign the consent form.

You may not qualify if:

• A clear history of central nervous system, cardiovascular system, renal, hepatic, pulmonary, metabolic, and musculoskeletal disorders or other notable diseases.
• Individuals with gastrointestinal disorders, such as history of hepatobiliary disease, history of gastrointestinal disease, history of gastrointestinal surgery (except appendectomy) or history of chronic pancreatitis or idiopathic acute pancreatitis, and those with habitual diarrhea.
• Previous tip-twisting ventricular tachycardia or other risk factors that can lead to malignant arrhythmias, or a family history of first-degree relatives (i.e., biological parents, siblings, or children) with short QT syndrome, long QT syndrome, unexplained sudden death, drowning, or sudden infant death syndrome in young adulthood (less than/equal to 40 years of age), or cardiac conduction block.
• Have disorders of electrolyte metabolism such as hyperkalemia, hypokalemia, hypomagnesemia, hypomagnesemia, hypercalcemia or hypocalcemia.
• If the results of vital signs (blood pressure, pulse, respiration, temperature) are abnormal and clinically significant, a retest is allowed to confirm the results if they are abnormal, and the abnormal values of each vital sign.
• Physical examination, laboratory tests, 12-lead electrocardiogram (ECG), abdominal ultrasound, calcitonin and chest radiographs (orthopantomograms) suggesting the presence of abnormalities judged by the investigator to be clinically significant (retesting was allowed once).
• Smokers who smoked an average of more than 5 cigarettes per day in the 3 months prior to screening or who could not give up smoking during their participation in the trial or who had a positive smoke test.
• Those who have participated in other clinical trials as a subject within 3 months prior to screening.
• Those who donated blood or blood products ≥400 mL within 3 months prior to screening.
• Those who cannot tolerate venipuncture and have a history of needle and blood sickness.

Sponsors & Collaborators

• Beijing Dongfang Biotech Co., Ltd.: lead

Study Sites (1)

Peking University Third Hospital drug clinical trial Institute

Beijing, Beijing Municipality, China

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Overweight

Interventions

Injections; Metformin; Rosuvastatin Calcium; Digoxin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics; Biguanides; Guanidines; Amidines; Organic Chemicals; Sulfonamides; Amides; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Glycosides; Carbohydrates

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 22, 2024
• First Posted: February 8, 2024
• Study Start: October 19, 2023
• Primary Completion: April 15, 2024
• Study Completion: April 15, 2024
• Last Updated: August 21, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)