Clinical trial NCT06247748: Influence of JY09 on Pharmacokinetics of Metformin , Rosuvastatin , and Digoxin and the QT Interval Study in Overweight Chinese Subjects
Official title: Evaluation of the Effects of Exendin-4 Fc Fusion Protein (JY09) Injection on the Pharmacokinetic Profiles of Metformin Hydrochloride Tablets, Rosuvastatin Calcium Tablets, and Digoxin Tablets and on the QT Interval in Overweight Chinese Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes Mellitus, Type 2
Overweight
Keywords: JY09
QT Interval
Lead sponsor: Beijing Dongfang Biotech Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-02-08
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: The Metformin Peak Concentration (Cmax )
timeFrame: 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)
measure: Area under the Metformin blood concentration-time curve
timeFrame: 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)
measure: The Rosuvastatin Peak Concentration (Cmax )
timeFrame: From time 0 to 96 hours after a single dose of Rosuvastatin without JY09 exposure (Day 8) and at JY09 steady state (Day 95)
measure: Area under the Rosuvastatin blood concentration-time curve
timeFrame: From time 0 to 96 hours after a single dose of Rosuvastatin without JY09 exposure (Day 8) and at JY09 steady state (Day 95)
measure: The Digoxin Peak Concentration (Cmax )
timeFrame: From time 0 to 168 hours after a single dose of Digoxin without JY09 exposure (Day 15) and at JY09 steady state (Day 102)
measure: Baseline-corrected difference of Corrected QT interval after multiple subcutaneous injections of JY09 injection
timeFrame: From time 0 to 72 hours after a single dose of JY09 (Day 22) and at JY09 steady state (Day 92)
Secondary outcomes:
measure: Safety endpoint-Adverse events
timeFrame: From baseline (Day -1) to follow-up (Day 123)
measure: Vital signs-Blood pressure
timeFrame: From baseline (Day -1) to follow-up (Day 123)
measure: Vital signs-Pulse
timeFrame: From baseline (Day -1) to follow-up (Day 123)
measure: Vital signs-Respiration
timeFrame: From baseline (Day -1) to follow-up (Day 123)
measure: Physical examination
timeFrame: From baseline (Day -1) to follow-up (Day 123)
measure: Laboratory tests-Routine blood
timeFrame: From baseline (Day -1) to follow-up (Day 123)
measure: Laboratory tests-Blood biochemistry
timeFrame: From baseline (Day -1) to follow-up (Day 123)
measure: Laboratory tests-Urine routine
timeFrame: From baseline (Day -1) to follow-up (Day 123)
measure: Laboratory tests-coagulation function
timeFrame: From baseline (Day -1) to follow-up (Day 123)
measure: 12-lead electrocardiogram (ECG)
timeFrame: From baseline (Day -1) to follow-up (Day 123)
measure: Immunogenicity
timeFrame: From baseline (Day -1) to follow-up (Day 123)
Other outcomes:
measure: Area Under the Effect Curve from time 0 to the last measurable concentration (AUEC0-t )
timeFrame: From time 0 to 240 minutes after Oral glucose(Day21) and Oral glucose(Day84).
measure: The Peak Effect Concentration(ECmax）
timeFrame: From time 0 to 240 minutes after Oral glucose(Day21) and Oral glucose(Day84).
measure: Maximum Effect Time(ETmax )
timeFrame: From time 0 to 240 minutes after Oral glucose(Day21) and Oral glucose(Day84).
measure: (AUEC0-t after JY09 administration - AUEC0-t before JY09 administration)/AUEClast before JY09 administration ×100%(Δ%AUEC0-t)
timeFrame: From time 0 to 240 minutes after Oral glucose(Day21) and Oral glucose(Day84).
measure: (post-administration Maximum Effect(Emax)- pre-administration Maximum Effect(Emax))/pre-administration Maximum Effect(Emax)×100%(Δ%Emax )
timeFrame: From time 0 to 240 minutes after Oral glucose(Day21) and Oral glucose(Day84).
measure: Body fat mass
timeFrame: Day19 or Day20,Day103 or Day104.
measure: Body fat percentage
timeFrame: Day19 or Day20,Day103 or Day104.
measure: Fat-free weight
timeFrame: Day19 or Day20,Day103 or Day104.
measure: Skeletal muscle mass
timeFrame: Day19 or Day20,Day103 or Day104.
measure: Waist-to-hip ratio
timeFrame: Day19 or Day20,Day103 or Day104.
measure: Visceral fat area
timeFrame: Day19 or Day20,Day103 or Day104.
measure: Pharmacodynamically relevant plasma endogenous markers（If necessary）
timeFrame: From time 0 to 72 hours after a single dose of JY09 (Day 22) and at JY09 steady state (Day 92) and Day21，Day29，Day43，Day83
measure: Pharmacodynamically relevant plasma metabolomics(if necessary)
timeFrame: From time 0 to 72 hours after a single dose of JY09 (Day 22) and at JY09 steady state (Day 92) and Day21，Day29，Day43，Day83
measure: Blood Cell Genotype Characterization (if necessary)
timeFrame: Day21，Day29，Day43，Day83
measure: Bacteria genus
timeFrame: Day21 or Day22,Day84 or Day85
measure: Relative abundance
timeFrame: Day21 or Day22,Day84 or Day85
Locations:
city: Beijing
country: China
facility: Peking University Third Hospital drug clinical trial Institute
state: Beijing
Study officials:
References: