Evaluation of the Pharmacokinetics of Microdose Midazolam, Dabigatran, Pitavastatin, Atorvastatin and Rosuvastatin in Diabetic Patients

NCT06273215 | Recruiting Phase 4

• 1 other identifier: DCTC-IIR202217
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

1.To explore the functional changes of P-gp, CYP3A4, OATP1B and BCRP in Diabetic patients (including the non-obese T2DM, obese T2DM, elderly T2DM, and T1DM).

Conditions

Diabetes

Outcome Measures

Primary Outcomes (1)

• Pharmacokinetics of study drug

  The plasma concentration of midazolam, dabigatran, pitavastatin, atorvastatin and rosuvastatin before dosing and 1 h, 4 h, 8 h and 24 h.

  Baseline and within 24 hours after administration

Secondary Outcomes (2)

• Concentration of endogenous markers of CYP3A and OATP

  Baseline

• Genotype of OATP and BCRP

  Baseline

Study Arms (4)

Non-obese T2DM

EXPERIMENTAL

Drug: The combinations of 10 µg midazolam, 375 µg dabigatran etexilate, 10 µg pitavastatin, 50 µg rosuvastatin, and 100 µg atorvastatin were administered to diabetic patients on an empty stomach.

Obese T2DM

EXPERIMENTAL

Drug: The combinations of 10 µg midazolam, 375 µg dabigatran etexilate, 10 µg pitavastatin, 50 µg rosuvastatin, and 100 µg atorvastatin were administered to diabetic patients on an empty stomach.

Elderly T2DM

EXPERIMENTAL

Drug: The combinations of 10 µg midazolam, 375 µg dabigatran etexilate, 10 µg pitavastatin, 50 µg rosuvastatin, and 100 µg atorvastatin were administered to diabetic patients on an empty stomach.

T1DM

EXPERIMENTAL

Drug: The combinations of 10 µg midazolam, 375 µg dabigatran etexilate, 10 µg pitavastatin, 50 µg rosuvastatin, and 100 µg atorvastatin were administered to diabetic patients on an empty stomach.

Interventions

The combinations of 10 µg midazolam, 375 µg dabigatran etexilate, 10 µg pitavastatin, 50 µg rosuvastatin, and 100 µg atorvastatin were administered to diabetic patients on an empty stomach. 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.

Elderly T2DM; Non-obese T2DM; Obese T2DM; T1DM

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All participants:
• \. Patients diagnosed with diabetes prior to trial screening and the duration was more than 1 year, but less than 20 years. Previous diagnostic indicators included, but were not limited to, fasting blood glucose (FBG) ≥7 mmol/L or HbA1c ≥6.5 %.
• \. Diabetes with other chronic diseases (e.g., hyperlipidemia or hypertension) but which are well-managed through diet or medication also can be included in study (e.g., systolic blood pressure \< 140 mmHg, diastolic blood pressure \< 90 mmHg, the low density lipoprotein cholesterol (LDL-C) \< 2.6 mmol/L).
• \. Signed the Inform Consent Form, fully understood the trial conduction and comply with the requirement of the research.
• Non-obese Type 2 Diabetes Mellitus (T2DM):
• Age between 18-65 (include).
• Body mass index (BMI) of 18.5 to 27.9 kg/m2 (include); body weight for male \>50 kg, for female \>45 kg; the proportion of a specific gender should be no less than one-third.
• Obese T2DM:
• Age between 18-65 (include).
• Body mass index (BMI) ≥ 28 kg/m2; body weight for male \>50 kg, for female \>45 kg; the proportion of a specific gender should be no less than one-third.
• Elderly T2DM:
• Age 75 years or older.
• Body mass index (BMI) of 18.5 to 27.9 kg/m2 (include); body weight for male \>50 kg, for female \>45 kg; the proportion of a specific gender should be no less than one-third.
• Type 1 Diabetes Mellitus (T1DM):
• Patients diagnosed with T1DM prior to trial screening and the duration was more than 1 year, but less than 20 years. Previous diagnostic indicators included, but were not limited to, diabetic patients who need lifelong insulin maintenance therapy or have ketoacidosis tendency or have type 1 diabetes-related autoantibodies (glutamic acid decarboxylase autoantibodies, islet cell antibodies, insulin antibodies, etc.).

You may not qualify if:

• All participants:
• \. Subjects fasting blood glucose ≥13.3 mmol/L or ≤3.9 mmol/L.
• \. Malignant tumor patient.
• \. History of stroke, chronic seizures, or other neurological disorders.
• \. Combined with serious systemic diseases, such as respiratory, blood, digestive, urinary system diseases.
• \. Participate in any other clinical trial within 3 months prior to the trial.
• \. Blood donation or blood loss ≥400mL or received blood product treatment within 8 weeks prior to the start of the trial.
• \. Family history of clinically significant ECG abnormalities or long QT syndrome.
• \. History of hypersensitive reaction or allergic to study drugs (including Midazolam, Dabigatran etexilate, Pitavastatin, Atorvastatin, and Rosuvastatin).
• \. Patients who could not discontinue the study drugs (including Midazolam, Dabigatran etexilate, Pitavastatin, Atorvastatin, and Rosuvastatin) within 3 days before the trial because of illness.
• \. Take weak/moderate inhibiters or inducers of CYP3A/BCRP/OATP1B/P-gp within 14 days before screening, including but not limited to: clarithromycin, boceprevir, cobicistat, danoprevir, grapefruit juice, indinavir, ketoconazole, telaprevir, paritaprevir, Telithromycin, troleandomycin, voriconazole, nafazodone, Idelalisib, nelfinavir, fluconazole, aprepitant, ciprofloxacin, conivaptan, crizotinib, cyclosporin A, diltiazem, fluvoxamine, imatinib, tofisopam, atazanavir, erythromycin, gemfibrozil, simeprevir, amiodarone, 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.
• \. Any condition that may significantly affect the absorption, distribution, metabolism, and excretion of glucose and study drugs, or any condition that may pose a hazard to the subject. Investigators were instructed on the following:
• (1) History of inflammatory bowel disease, gastritis, ulcers, gastrointestinal or rectal bleeding.
• (2) History of major gastrointestinal surgery (e.g., gastrectomy, gastrostomy, or enterectomy).
• (3) Liver function tests (such as ALT, AST) are abnormal and clinically significant, indicating liver disease.

Sponsors & Collaborators

• Peking University Third Hospital: lead

Study Sites (1)

Peking University Third Hospital

Beijing, Beijing Municipality, 100191, China

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus

Interventions

Midazolam; Dabigatran; pitavastatin; Rosuvastatin Calcium

Condition Hierarchy (Ancestors)

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

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

Central Study Contacts

Dongyang Liu

CONTACT

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

Yafen Li

CONTACT

18222566785; liyafen314159@163.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 12, 2024
• First Posted: February 22, 2024
• Study Start: March 5, 2023
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: February 22, 2024

Record last verified: 2024-02

Locations

CN (1)