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

Type 2 Diabetes Mellitus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05497674
• Other study ID #: DJT1116PG-DM-108
• Status: Completed
• Phase: Phase 1
• Start date: February 21, 2022
• Est. completion date: February 24, 2023

Study information

• Verified date: February 2023
• Source: Sunshine Lake Pharma Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: February 24, 2023
• Est. primary completion date: July 22, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Rongliflozin
oral administration, single dose on Day 1 and Day 11
• Rifampin
QD for 10 days
• Rongliflozin
oral administration, single dose on Day 1 and Day 6
• Probenecid
twice a day, for 5 days

Locations

Country	Name	City	State
China	The First Hospital of Jilin University	Jilin	Changchun

Sponsors (1)

Lead Sponsor	Collaborator
Sunshine Lake Pharma Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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