Effects of Rifampicin and Probenecid On The Pharmacokinetic Profile Of Rongliflozin In Healthy Subjects

Study Overview
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Brief Summary
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This is a phase I, open-label, fixed-sequence study in healthy Chinese subjects, performed at a single study centre. Cohort A will assess the Pharmacokinetic (PK) profile of rongliflozin when administered alone and the combination with rifampicin; Cohort B will assess the PK profile of rongliflozin when administered alone and combination with probenecid.

Official Title
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A Study In Healthy Subjects To Assess The Effects Of Rifampicin Capsules and Probenecid Tablets On The Pharmacokinetic Profile Of Rongliflozin Capsules

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Rongliflozin
* Drug: Rifampin
* Drug: Rongliflozin
* Drug: Probenecid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Sign the informed consent form before the trial and fully understand the trial content, process and possible adverse reactions; Be able to complete the test according to the requirements of the protocol; Subjects (including partners) are willing to take effective contraceptive measures from screening to 6 months after the last dose of drug administration; Male subjects weigh at least 50 kg and female subjects at least 45 kg. Body mass index (BMI) = weight (kg)/height 2 (m2), BMI within the range of 18 to 28 kg/m2 ; Physical examination and vital signs are both normal or do not have clinical significance. Exclusion Criteria: Smoking more than 5 cigarettes per day; Those who are allergic to or have allergies to the test drug; have a history of drug or alcohol abuse; Blood donation or massive blood loss (>450 mL) within three months prior to screening; Difficulty swallowing or any history of digestive system diseases which could affect drug absorption and excretion within 6 months before screening; taking any drugs that could alter liver enzyme activity, such as barbiturates, rifampin, etc., within 30 days before screening; have taken any prescription, over-the-counter, vitamin product or herbal medicine within 14 days prior to screening; Have taken special diets (including dragon fruit, mango, grapefruit, etc.) or exercised strenuously within 2 weeks before screening; Take an inhibitor or inducer of glucuronide transferase (UGT), P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP), such as itraconazole, ketoconazole, or dronedarone, within 30 days before screening; Significant changes in dietary or exercise habits within 2 weeks prior to screening; Female subjects are breastfeeding or have a positive blood pregnancy result during the screening period; During the screening period, the serum uric acid level was >420 µmol/l, or had a history of gout; during the screening period, the estimated glomerular filtration rate (eGFR) was <90 ml/min/1.73m2) or had a history of kidney stones or bladder stones (applicable to Cohort B); have a clinically significant laboratory tests or medical history; Positive for hepatitis B, hepatitis C, AIDS, syphilis; positive for urine drug test; History of urinary tract infection or genital infection before 6 months Those who participated in any drug clinical trial and used the experimental drug 3 months ago; Subjects with other factors deemed inappropriate by the investigator.

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rongliflozin and/or rifampicin<br>on Day 1, subjects will receive a single dose administration of rongliflozin, followed by a washout period of 4 days. Starting On Day 5, subjects will administer rifampicin once a day (QD) for 10 consecutive days ( Day 5 to Study Day 14) , comprising of a single dose administration of rongliflozin on Study Day 11. | Drug: Rongliflozin<br>* oral administration, single dose on Day 1 and Day 11<br>Drug: Rifampin<br>* QD for 10 days<br>|
| Experimental: rongliflozin and/or probenecid<br>on Day 1, subjects will receive a single dose administration of rongliflozin, followed by a washout period of 4 days. Probenecid will be administrated twice a day from Day 5 to Day 9, and another single dose administration of rongliflozin on Day 6. | Drug: Rongliflozin<br>* oral administration, single dose on Day 1 and Day 6<br>Drug: Probenecid<br>* twice a day, for 5 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| rongliflozin: area under the drug-time curve (AUC) ratios of geometric means of rongliflozin+rifampicin relative to rongliflozin alone. | To assess the effect of rifampicin on the AUC of rongliflozin | from 0 hour（pre-dose,within 30mins）to 5 days after rongliflozin dosing | 
| rongliflozin: The peak concentration (Cmax) ratios of geometric means of rongliflozin+rifampicin relative to rongliflozin alone. | To assess the effect of rifampicin on the Cmax of rongliflozin | from 0 hour（pre-dose,within 30mins）to 5 days after rongliflozin dosing | 
| rongliflozin: AUC ratios of geometric means of rongliflozin+probenecid relative to rongliflozin alone. | To assess the effect of probenecid on the AUC of rongliflozin | from 0 hour（pre-dose,within 30mins）to 5 days after rongliflozin dosing | 
| rongliflozin:Cmax ratios of geometric means of rongliflozin+probenecid relative to rongliflozin alone. | To assess the effect of probenecid on the Cmax of rongliflozin | from 0 hour（pre-dose,within 30mins）to 5 days after rongliflozin dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The time to peak (Tmax) of Rongliflozin. | To assess the effect of rifampicin and probenecid on the Tmax of rongliflozin | from 0 hour（pre-dose,within 30mins）to 5 days after rongliflozin dosing | 
| pharmacology (PD) of rongliflozin: cumulative urine glucose excretion every 24 hours | evaluate the cumulative urine glucose excretion every 24 hours after rongliflozin administration. | from 0 hour to 5 days after rongliflozin dosing | 
| the number of participants with adverse events (AE) in Cohort A | To evaluate the safety and tolerability of single dose of rongliflozin and combination of rifampin | from screening to 3 days after last dose of rifampicin | 
| the number of participants with adverse events (AE) in Cohort B | To evaluate the safety and tolerability of single dose of rongliflozin and combination of probenecid | from screening to 3 days after last dose of probenecid |