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

NCT05497674 | Completed Phase 1

• 1 other identifier: DJT1116PG-DM-108
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

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.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (4)

• The time to peak (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

  from 0 hour to 5 days after rongliflozin dosing

• the number of participants with adverse events (AE) in Cohort A

  from screening to 3 days after last dose of rifampicin

• the number of participants with adverse events (AE) in Cohort B

  from screening to 3 days after last dose of probenecid

Study Arms (2)

rongliflozin and/or rifampicin

EXPERIMENTAL

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; Drug: Rifampin

rongliflozin and/or probenecid

EXPERIMENTAL

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; Drug: Probenecid

Interventions

Rongliflozin DRUG

oral administration, single dose on Day 1 and Day 11

rongliflozin and/or rifampicin

Rifampin DRUG

QD for 10 days

rongliflozin and/or rifampicin

Probenecid DRUG

twice a day, for 5 days

rongliflozin and/or probenecid

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Sunshine Lake Pharma Co., Ltd.: lead

Study Sites (1)

The First Hospital of Jilin University

Jilin, Changchun, 130000, China

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

rongliflozin; Rifampin; Probenecid

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 1, 2022
• First Posted: August 11, 2022
• Study Start: February 21, 2022
• Primary Completion: July 22, 2022
• Study Completion: February 24, 2023
• Last Updated: March 1, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)