A Clinical Study to Evaluate the Pharmacokinetics of Microdose Midazolam, Dabigatran, Pitavastatin, Atorvastatin and Rosuvastatin in Healthy Volunteers and Renal Impairment Patients

NCT05747768 | Unknown Phase 4

• 1 other identifier: DCTC-IIR202229
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

1. 1.To explore the functional changes of P-gp, CYP3A4, OATP1B and BCRP in Chinese people with renal impairment;
2. 2.To explore the effect of dialysis on the functional changes of P-gp, CYP3A4, OATP1B and BCRP in patients with end-stage renal disease;
3. 3.Validation of urotoxic molecules as possible biomarkers that can assess intestinal P-gp function.

Conditions

Chronic Kidney Disease

Outcome Measures

Primary Outcomes (2)

• plasma concentration

  Baseline and within 24 hours after administration

• dialysate concentration

  1 day

Secondary Outcomes (2)

• biomarker concentration

  Baseline and within 24 hours after administration

• urine concentration

  Baseline

Study Arms (5)

Healthy Volunteers

EXPERIMENTAL

Healthy volunteer received drug combinations（10 µg midazolam, 375 µg dabigatran etexilate, 10 µg pitavastatin, 50 µg rosuvastatin, and 100 µg atorvastatin） on an empty stomach

Drug: Midazolam, dabigatran etexilate, pitavastatin, rosuvastatin and atorvastatin

Patients with mild-to-moderate renal impairment

EXPERIMENTAL

Patients with mild-to-moderate renal impairment received drug combinations（10 µg midazolam, 375 µg dabigatran etexilate, 10 µg pitavastatin, 50 µg rosuvastatin, and 100 µg atorvastatin） on an empty stomach

Drug: Midazolam, dabigatran etexilate, pitavastatin, rosuvastatin and atorvastatin

Patients with moderate to severe renal impairment

EXPERIMENTAL

Patients with moderate to severe renal impairment received drug combinations（10 µg midazolam, 375 µg dabigatran etexilate, 10 µg pitavastatin, 50 µg rosuvastatin, and 100 µg atorvastatin） on an empty stomach

Drug: Midazolam, dabigatran etexilate, pitavastatin, rosuvastatin and atorvastatin

Patients with severe renal impairment

EXPERIMENTAL

Patients with severe renal impairment received drug combinations（10 µg midazolam, 375 µg dabigatran etexilate, 10 µg pitavastatin, 50 µg rosuvastatin, and 100 µg atorvastatin） on an empty stomach

Drug: Midazolam, dabigatran etexilate, pitavastatin, rosuvastatin and atorvastatin

Patients with end-stage renal disease

EXPERIMENTAL

Patients with end-stage renal disease received drug combinations（10 µg midazolam, 375 µg dabigatran etexilate, 10 µg pitavastatin, 50 µg rosuvastatin, and 100 µg atorvastatin） on an empty stomach

Drug: Midazolam, dabigatran etexilate, pitavastatin, rosuvastatin and atorvastatin

Interventions

Midazolam, dabigatran etexilate, pitavastatin, rosuvastatin and atorvastatin DRUG

Midazolam, dabigatran etexilate, pitavastatin, rosuvastatin and atorvastatin were provided by the Department of Pharmacy, Peking University Third Hospital, and were dissolved and mixed with normal saline respectively, and the mixing process needed to be fully stirred. Then, according to the concentration of the drug mixed solution, the corresponding volume of mixed solution was given to achieve the dosage of 10 μg midazolam, 375 μg dabigatran etexilate, 10 μg pitavastatin, 50 μg rosuvastatin and 100 μg atorvastatin. In order to avoid the food effect, the test drugs were administered on an empty stomach on the administration day in this experiment.

Healthy Volunteers; Patients with end-stage renal disease; Patients with mild-to-moderate renal impairment; Patients with moderate to severe renal impairment; Patients with severe renal impairment

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All participants:
• male or female , Chinese (individuals have Chinese descent) subjects, Age between 18-65 (include) with the ability of cognizance;
• body mass index (BMI) of 18.5 to 24 kg/m2 for all participants ; body weight for male \>50 kg; a total body weight for female \>45 kg;
• female must be non-pregnant, non-breast feeding and if she is reproductive potential: must agree to use (and/have their partner use) effective methods of birth control beginning at screening ,throughout the study and until 6 months after last dosing of study drug;
• is a non-smoker or moderate smoker (≤20 cigarettes/day or the equivalent);
• signed the Inform Consent Form , fully understood the trial conduction and comply with the requirement of the research;
• Participants with mild to moderate , moderate to severe , severe renal impairment or end stage renal disease:
• has a clinical diagnosis of renal impairment and meets the protocol-specified renal impairment function qualifications at screening;
• with the classification of KDIGO (Kidney Disease Improving Global Outcomes ), the mild to moderate renal impairment patients have eGFR between 45 to 90(include) mL/min/1.73m2 based on MDRD (Modification of Diet in Renal Disease Study) equation, without dialysis before;
• with the classification of KDIGO (Kidney Disease Improving Global Outcomes ), the moderate to severe renal impairment patients have eGFR between 30 to 44(include) mL/min/1.73m2 based on MDRD(Modification of Diet in Renal Disease Study) equation, without dialysis before;
• with the classification of KDIGO (Kidney Disease Improving Global Outcomes ), The moderate to severe renal impairment patients have eGFR between 15 to 29(include) mL/min/1.73m2 based on MDRD(Modification of Diet in Renal Disease Study) equation, without dialysis before;
• with the classification of KDIGO (Kidney Disease Improving Global Outcomes ), The end stage renal disease patients have eGFR below 15 (include) mL/min/1.73m2 based on MDRD(Modification of Diet in Renal Disease Study) equation, with dialysis therapy;
• participants with mild to moderate , moderate to severe , severe renal impairment or end stage renal disease: With stable renal function lasted for three months before first oral dose ; the shrinkage of eGFR be within 30%;
• Healthy participants ,besides:
• has baseline eGFR ≥ 90 mL/min based on MDRD (Modification of Diet in Renal Disease Study) equation;

You may not qualify if:

• is mentally or legally incapacitated at the time of the screening visit or expected during the conduct of the study;
• history of stroke, chronic seizures, or major neurological disorders;
• history of malignant neoplastic disease;
• history or presence of alcoholism or drug abuse within the past 6 months;
• history of hypersensitive reaction or allergic to study drug (including midazolam, dabigatran Etexilate, pitavastatin, atorvastatin, rosuvastatin), only if with researchers permission;
• blood donation within the past 4 weeks or lost more than 500 mL blood before screening;
• apheresis within the past 8 weeks before screening;
• take weak/moderate inhibiters or inducers of CYP3A/BCRP/OATP1B/P-gp within 14 days before screening, including but not limited to: clarithromycin, boceprevir, cobicistatdanoprevir, grapefruit juice, indinavir, ketoconazole, telaprevir, paritaprevir, Telithromycin, troleandomycin, voriconazole, nafazodone, Idelalisib, nelfinavir, fluconazole, aprepitant, ciprofloxacin, conivaptan , crizotinib, cyclosporin A, diltiazem, fluvoxamine, imatinib, tofisopam, atazanavir, erythromycingemfibrozilsimepreviramiodarone, carvedilol, itraconazole, lapatinib, lopinavir, ritonavir, propafenone, quinidine, ranolazine, saquinavir, telaprevir, verapamil, tipranavir, curcumin, Eltrombopag, phenytoin, rifampicin, apalutamide, carbamazepine, St. John's Wort, mitotan, enzalutamide, bosentan, efavirenz, primidone, phenobarbital;
• intolerance of venous blood collection;
• history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, immunological, respiratory, or genitourinary abnormalities or diseases, include cancer, traumatic brain injury, persistent viral infection, rheumatoid arthritis, inflammatory bowel disease, NAFLD, Liver cirrhosis, HIV, Hyperthyreosis, Cushing syndrome, Parkinson or has a history of Parkinson in his family;
• history of myocardial infarction, cerebral stroke, cerebral infarction within 3 months;
• history of gastrointestinal diseases: irritable bowel syndrome, enteric bacterial overgrowth syndrome, gastroesophageal reflux disease, Gallstones, coeliac disease, Crohn disease, Ulcerative Colitis, active peptic ulcers;
• subjects who test positive at screening for human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis B surface antigen (HbsAg), and syphilis;
• history of renal transplant or nephrectomy;
• presence of uncontrolled type 2 diabetes mellitus (T2DM), a history of type 1 diabetes or ketoacidosis;

Sponsors & Collaborators

• Peking University Third Hospital: lead

Study Sites (1)

Peking University Third Hospital

Beijing, China

RECRUITING

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Interventions

Midazolam; Dabigatran; pitavastatin; Rosuvastatin Calcium; Atorvastatin

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Benzimidazoles; Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Pyrroles; Azoles; Heptanoic Acids; Fatty Acids; Lipids

Central Study Contacts

Dongyang Liu

CONTACT

(86)010-82266658; liudongyang@vip.sina.com

Hao Liang

CONTACT

13426217031; lianghao86@126.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Researcher

Study Record Dates

• First Submitted: February 6, 2023
• First Posted: February 28, 2023
• Study Start: July 15, 2022
• Primary Completion: June 1, 2024
• Study Completion: December 31, 2024
• Last Updated: February 28, 2023

Record last verified: 2023-02

Locations

CN (1)