Clinical trial NCT05497674: Effects of Rifampicin and Probenecid On The Pharmacokinetic Profile Of Rongliflozin In Healthy Subjects
Official title: A Study In Healthy Subjects To Assess The Effects Of Rifampicin Capsules and Probenecid Tablets On The Pharmacokinetic Profile Of Rongliflozin Capsules
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Sunshine Lake Pharma Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2022-08-11
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: rongliflozin: area under the drug-time curve (AUC) ratios of geometric means of rongliflozin+rifampicin relative to rongliflozin alone.
timeFrame: from 0 hour（pre-dose,within 30mins）to 5 days after rongliflozin dosing
measure: rongliflozin: The peak concentration (Cmax) ratios of geometric means of rongliflozin+rifampicin relative to rongliflozin alone.
timeFrame: from 0 hour（pre-dose,within 30mins）to 5 days after rongliflozin dosing
measure: rongliflozin: AUC ratios of geometric means of rongliflozin+probenecid relative to rongliflozin alone.
timeFrame: from 0 hour（pre-dose,within 30mins）to 5 days after rongliflozin dosing
measure: rongliflozin:Cmax ratios of geometric means of rongliflozin+probenecid relative to rongliflozin alone.
timeFrame: from 0 hour（pre-dose,within 30mins）to 5 days after rongliflozin dosing
Secondary outcomes:
measure: The time to peak (Tmax) of Rongliflozin.
timeFrame: from 0 hour（pre-dose,within 30mins）to 5 days after rongliflozin dosing
measure: pharmacology (PD) of rongliflozin: cumulative urine glucose excretion every 24 hours
timeFrame: from 0 hour to 5 days after rongliflozin dosing
measure: the number of participants with adverse events (AE) in Cohort A
timeFrame: from screening to 3 days after last dose of rifampicin
measure: the number of participants with adverse events (AE) in Cohort B
timeFrame: from screening to 3 days after last dose of probenecid
Other outcomes:
Locations:
city: Jilin
country: China
facility: The First Hospital of Jilin University
state: Changchun
Study officials:
References: