Effects of Rifampicin and Probenecid On The Pharmacokinetic Profile Of Rongliflozin In Healthy Subjects
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: rongliflozin and/or rifampicin 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
oral administration, single dose on Day 1 and Day 11
Drug: Rifampin
QD for 10 days
|
| Experimental: rongliflozin and/or probenecid 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
oral administration, single dose on Day 1 and Day 6
Drug: Probenecid
twice a day, for 5 days
|
Outcome Measures
Primary Outcome Measures
- rongliflozin: area under the drug-time curve (AUC) ratios of geometric means of rongliflozin+rifampicin relative to rongliflozin alone. [from 0 hour（pre-dose,within 30mins）to 5 days after rongliflozin dosing]
To assess the effect of rifampicin on the AUC of rongliflozin
- rongliflozin: The peak concentration (Cmax) ratios of geometric means of rongliflozin+rifampicin relative to rongliflozin alone. [from 0 hour（pre-dose,within 30mins）to 5 days after rongliflozin dosing]
To assess the effect of rifampicin on the Cmax of rongliflozin
- rongliflozin: AUC ratios of geometric means of rongliflozin+probenecid relative to rongliflozin alone. [from 0 hour（pre-dose,within 30mins）to 5 days after rongliflozin dosing]
To assess the effect of probenecid on the AUC of rongliflozin
- rongliflozin:Cmax ratios of geometric means of rongliflozin+probenecid relative to rongliflozin alone. [from 0 hour（pre-dose,within 30mins）to 5 days after rongliflozin dosing]
To assess the effect of probenecid on the Cmax of rongliflozin
Secondary Outcome Measures
- The time to peak (Tmax) of Rongliflozin. [from 0 hour（pre-dose,within 30mins）to 5 days after rongliflozin dosing]
To assess the effect of rifampicin and probenecid on the Tmax of rongliflozin
- pharmacology (PD) of rongliflozin: cumulative urine glucose excretion every 24 hours [from 0 hour to 5 days after rongliflozin dosing]
evaluate the cumulative urine glucose excretion every 24 hours after rongliflozin administration.
- the number of participants with adverse events (AE) in Cohort A [from screening to 3 days after last dose of rifampicin]
To evaluate the safety and tolerability of single dose of rongliflozin and combination of rifampin
- the number of participants with adverse events (AE) in Cohort B [from screening to 3 days after last dose of probenecid]
To evaluate the safety and tolerability of single dose of rongliflozin and combination of probenecid
Eligibility Criteria
Criteria
Inclusion Criteria:
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Sign the informed consent form before the trial and fully understand the trial content, process and possible adverse reactions;
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Be able to complete the test according to the requirements of the protocol;
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Subjects (including partners) are willing to take effective contraceptive measures from screening to 6 months after the last dose of drug administration;
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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 ;
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Physical examination and vital signs are both normal or do not have clinical significance.
Exclusion Criteria:
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Smoking more than 5 cigarettes per day;
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Those who are allergic to or have allergies to the test drug;
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have a history of drug or alcohol abuse;
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Blood donation or massive blood loss (>450 mL) within three months prior to screening;
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Difficulty swallowing or any history of digestive system diseases which could affect drug absorption and excretion within 6 months before screening;
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taking any drugs that could alter liver enzyme activity, such as barbiturates, rifampin, etc., within 30 days before screening;
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have taken any prescription, over-the-counter, vitamin product or herbal medicine within 14 days prior to screening;
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Have taken special diets (including dragon fruit, mango, grapefruit, etc.) or exercised strenuously within 2 weeks before screening;
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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;
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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;
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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);
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have a clinically significant laboratory tests or medical history;
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Positive for hepatitis B, hepatitis C, AIDS, syphilis; positive for urine drug test;
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History of urinary tract infection or genital infection before 6 months
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Those who participated in any drug clinical trial and used the experimental drug 3 months ago;
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Subjects with other factors deemed inappropriate by the investigator.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The First Hospital of Jilin University | Jilin | Changchun | China | 130000 |
Sponsors and Collaborators
- Sunshine Lake Pharma Co., Ltd.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- DJT1116PG-DM-108