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

NCT ID: NCT06247748

Last Updated: 2024-08-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-10-19
• Study Completion Date: 2024-04-15

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Exendin-4 Fc fusion protein (JY09) injection

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.

Group Type: EXPERIMENTAL

Exendin-4 Fc fusion protein (JY09) injection

Intervention Type: 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.

Metformin Hydrochloride tablet

Intervention Type: 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).

Rosuvastatin calcium tablets

Intervention Type: 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.

Digoxin tablet

Intervention Type: 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)

Interventions

Exendin-4 Fc fusion protein (JY09) injection

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.

Intervention Type: DRUG

Metformin Hydrochloride tablet

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).

Intervention Type: DRUG

Rosuvastatin calcium tablets

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.

Intervention Type: DRUG

Digoxin tablet

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)

Intervention Type: DRUG

Other Intervention Names

JY09; Metformin; Rosuvastatin; digoxin

Eligibility Criteria

Inclusion Criteria

1. 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).

2. 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 ).

3. 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.

4. 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.

5. Understand the content of the informed consent form, agree to participate in this trial and voluntarily sign the consent form.

Exclusion Criteria

1. A clear history of central nervous system, cardiovascular system, renal, hepatic, pulmonary, metabolic, and musculoskeletal disorders or other notable diseases.

2. 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.

3. 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.

4. Have disorders of electrolyte metabolism such as hyperkalemia, hypokalemia, hypomagnesemia, hypomagnesemia, hypercalcemia or hypocalcemia.

5. 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.

6. 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).

7. 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.

8. Those who have participated in other clinical trials as a subject within 3 months prior to screening.

9. Those who donated blood or blood products ≥400 mL within 3 months prior to screening.

10. Those who cannot tolerate venipuncture and have a history of needle and blood sickness.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Beijing Dongfang Biotech Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Peking University Third Hospital drug clinical trial Institute

Beijing, Beijing Municipality, China

Countries

China

Other Identifiers

dfbt-jy09-ow-2023-101

Identifier Type: -

Identifier Source: org_study_id