Drug Drug Interaction (DDI) Between Supaglutide and Digoxin or Metformin

Study Overview
=================
Brief Summary
-----------------
This is a study of a drug drug interaction between Supaglutide and Digoxin or Metformin.

Detailed Description
-----------------
This is a single-centre, open labeled, fixed-sequence study designed to assess the pharmacokinetic effects of multiple subcutaneous injections of Supalutide on a single oral dose of digoxin or multiple oral doses of metformin. 32 healthy subjects are planned to be enrolled and allocated to 2 parallel trial groups, Digoxin combined with Sulpalutide injection (Group A) and Metformin combined with Sulpalutide injection (Group B), with 16 cases in each group, of which no less than 4 were of a single sex.

Official Title
-----------------
A Single-centre, Open Labeled, Fixed-sequence Study to Evaluate the Effect of Supaglutide on Digoxin or Metformin Pharmacokinetics

Conditions
-----------------
Healthy Volunteers

Intervention / Treatment
-----------------
* Drug: Supaglutide injection
* Drug: Digoxin
* Drug: Metformin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy Chinese subjects. Age between 18 and 45 years, inclusive. Body mass index [BMI = weight (kg)/height2 (m2)] of between 20 and 28 kg/m2 (including thresholds), with male subjects weighing no less than 50 kg and female subjects weighing no less than 45 kg. Subjects with no plan of pragnancy within the screening period up to 3 months after the last dose and who are voluntarily using contraception. 6. Subjects who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures. Exclusion Criteria: Subjects with a previous or existing history of serious cardiac, hepatic, renal, gastrointestinal, neurological, psychiatric abnormalities and metabolic abnormalities. Subjects with a previous or existing disease affecting the absorption, distribution, metabolism or excretion of drugs, such as active peptic ulcers or bleeding, history of ulcers or bleeding, acute and chronic pancreatitis, etc. Subjects with a history or family history of C-cell tumours/carcinoma of the thyroid gland, or a previous history of thyroid insufficiency or thyroid hormone abnormalities Subjects who have undergone major surgery within 4 weeks prior to screening which, in the judgment of the investigator, may affect this trial, such as gastric and duodenal surgery, cholecystectomy, nephrectomy, or removal of malignant tumours (except for previous appendectomy), or those who are scheduled to undergo major surgery during the trial those with existing symptoms of unexplained infection.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A: Digoxin combined with Supaglutide group<br>Subjects will receive a single oral dose of 0.25 mg digoxin tablets on Day 1. And will received subcutaneous injection of sulpalutide QW for five weeks（D5-D33）. Then receive another single oral dose of 0.25 mg digoxin tablets on Day 35. | Drug: Supaglutide injection<br>* Administered subcutaneously in the Supaglutide arms<br>* Other names: Diabegone;Drug: Digoxin<br>* Digoxin<br>|
| Experimental: Group B: Metformin combined with Supaglutide Group<br>Subjects will receive multiple oral dose of Metformin tablets on Day 1-3. And will received subcutaneous injection of sulpalutide QW for five weeks（D5-D33）. Then receive another round of Metformin tablets on Day 32-34. | Drug: Supaglutide injection<br>* Administered subcutaneously in the Supaglutide arms<br>* Other names: Diabegone;Drug: Metformin<br>* Metformin<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Group A: Plasma Cmax of digoxin | when given in combination with supaglutide in healthy volunteers | 39 Days | 
| Group A: Plasma AUC0-last of digoxin | when given in combination with suplaglutide in healthy volunteers | 39 Days | 
| Group A: Plasma AUC0-inf of digoxin | when given in combination with supaglutide in healthy volunteers | 39 Days | 
| Group B: Plasma Cmax,ss of Metformin | when given in combination with supaglutide in healthy volunteers | 34 Days | 
| Group B: Plasma AUC0-tau of Metformin | when given in combination with suplaglutide in healthy volunteers | 34 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Group A: Plasma Tmax of Digoxin | when given in combination with supaglutide in healthy volunteers | 39 Days | 
| Group A: Plasma t1/2 of digoxin | when given in combination with supaglutide in healthy volunteers | 39 Days | 
| Group A: Plasma CL/F of digoxin | when given in combination with suplaglutide in healthy volunteers | 39 Days | 
| Group A: Plasma Vz/F of digoxin | when given in combination with supaglutide in healthy volunteers | 39 Days | 
| Group B: Plasma Tmax of Metformin | when given in combination with supaglutide in healthy volunteers | 34 Days | 
| Group B: Plasma Cmin,ss of Metformin | when given in combination with suplaglutide in healthy volunteers | 34 Days | 
| Group B: Plasma t1/2 of Metformin | when given in combination with suplaglutide in healthy volunteers | 34 Days | 
| Group B: Plasma CL/F of Metformin | when given in combination with suplaglutide in healthy volunteers | 34 Days | 
| Group B: Plasma Vz/F of metformin | when given in combination with suplaglutide in healthy volunteers | 34 Days |