A Clinical Trial to Evaluate the Safety and the Pharmacokinetic Interaction of Telmisartan and Dapagliflozin.

A Two-arm, Open-label, Single-sequence, Multiple Oral Dosings, Crossover Clinical Trial to Evaluate the Safety and the Pharmacokinetic Interaction of THP-00101 and THP-00102 in Healthy Adult Volunteers

The study was designed to evaluate the safety and pharmacokinetic interaction between THP-00101 and THP-00102 in healthy adult volunteers.

Study Overview

• Status: Completed
• Conditions: Hypertension; Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: THP-00101 (Dapagliflozin) 10mg; Drug: THP-00102 (Telmisartan) 80mg

Detailed Description

The study consists of 2 periods of THP-00101 or THP00102 administration over 5 days and combined administration of THP-00101 and THP00102 over 5 days in two arms.

Dapagliflozin (18 Subjects): Tx A (5 days) -> Tx B (5 days) Treatment A: THP-00101 (Dapagliflozin) 1 tablet/5 days Treatment B: THP-00101 (Dapagliflozin) 1 tablet/5 days + THP-00102 (Telmisartan) 1 tablet/5 days

Telmisartan (32 Subjects): Tx C (5 days) -> Tx C (5 days) Treatment C: THP-00102 (Telmisartan) 1 tablet/5 days Treatment B: THP-00102 (Telmisartan) 1 tablet/5 days + THP-00101 (Dapagliflozin) 1 tablet/5 days

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 08779
    • H Plus Yangji Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. A person who is 19 years of age or older at the screening visit

2. A person who weighs at least 55 kg (50 kg for women) and has a body mass index (BMI) of at least 18.0 kg/m2 and at least 30.0 kg/m2 at screening visit

   ☞ BMI (kg/m2) = Weight (kg)/ {Height (m)}2

3. A person who has no clinically meaningful congenital or chronic disease and has no pathological symptoms or findings as a result of medical examination at a screening visit
4. A person who has been determined to be suitable for the test as a result of diagnostic tests such as hematology tests, hematochemical tests, serum tests, urine tests, etc., set and conducted by the test manager (or delegated test doctor) according to the characteristics of clinical drugs

5. A person who agrees to exclude the possibility of pregnancy using a medically recognized contraceptive method* (except hormones) and does not provide sperm or eggs from the date of first administration of the clinical trial drug to 14 days after the date of last clinical trial drug administration

   *medically-accepted Contraceptive methods: a combination of intrauterine devices, vasectomy, tubular ligation, and blocking contraception (male condoms, female condoms, cervical caps, contraceptive septum, sponge, etc.) or a combination of two or more blocking contraceptives

6. A person who has received and understood sufficient explanation of the purpose, contents, characteristics of clinical trial drugs, expected abnormal cases, etc., and signed the consent form according to his/her free will

Exclusion Criteria:

1. A person who has or has a history of clinically significant diseases corresponding to the digestive system, cardiovascular system, endocrine system, respiratory system, blood and tumor, infectious disease, kidney and urinary system, mental and nervous system, musculoskeletal system
2. A person who has a history of gastrointestinal surgery (excluding simple appendectomy or hernia surgery) or has gastrointestinal diseases that may affect drug absorption
3. Those who have taken drug metabolism-inducing and inhibiting drugs such as barbital drugs within one month of the first administration date, or drugs that may interfere with this clinical trial within 10 days of the first administration (however, in consideration of pharmacokinetic and pharmacokinetic characteristics of combination drugs it may consider as possible)
4. A person who participates in other clinical trials or biological equivalence tests within six months of the first administration and administered clinical trial drugs
5. A person who has donated whole blood within 8 weeks of the first administration, donated ingredients within 2 weeks or received a blood transfusion within 4 weeks from the first administration

6. A person who meets the following conditions within one month of the first dose date

   • Men consume an average of 21 cups/week of alcohol

   • Women consume an average of 14 cups/week of alcohol

     (1 glass = 50mL of soju, 30mL of spirits, or 250mL of beer)

   • An average of more than 20 cigarettes a day

7. A patient who falls under the following

   • Patients with a history of hypersensitivity to the main ingredient or additive of this drug
   • Type 1 diabetes patient with diabetic ketoacidosis
   • Patients with genetic problems such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption
   • A patient on dialysis
   • Patients with severe liver disorders, biliary obstruction, or bile congestion (mostly this drug is excreted as bile). A decrease in liver cleaning rate can be expected in patients with bile congestion, biliary obstruction disease, or liver failure.)
   • Patients with hereditary angioedema, or patients with a history of angioedema when treated with ACE inhibitors or angiotensin II receptor antagonists
   • Combination with aliskiren-containing preparations in patients with diabetes or moderate to severe renal disabilities (glomerular filtration rate <60mL/min/1.73m2)
8. For reasons other than the above selection and exclusion criteria, the person in charge of testing (or the delegated test doctor) determines that he/she is not suitable for participation in this clinical trial
9. In the case of female volunteers, those suspected of being pregnant or nursing

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dapagliflozin; THP-00101 (Dapagliflozin) 10mg (18 Subjects): Tx A (5 days) -> Tx B (5 days) Treatment A: THP-00101 (Dapagliflozin) 10mg/5 days Treatment B: THP-00101 (Dapagliflozin) 10mg/5 days + THP-00102 (Telmisartan) 80mg/5 days	Drug: THP-00101 (Dapagliflozin) 10mg; Dapagliflozin 10mg Tablet / 5 days in period 1 and period 2 will be given to Arm A Dapagliflozin 10mg Tablet / 5 days in period 2 will be given to Arm B; Other Names: Forxiga Tab. 10mg; Drug: THP-00102 (Telmisartan) 80mg; Telmisartan 80mg Tablet / 5 days in period 1 and period 2 will be given to Arm B Telmisartan 80mg Tablet / 5 days in period 2 will be given to Arm A; Other Names: Micardis Tab. 80mg
Experimental: Telmisartan; THP-00102 (Telmisartan) 80mg (32 Subjects): Tx C (5 days) -> Tx B (5 days) Treatment C: THP-00102 (Telmisartan) 80mg/5 days Treatment B: THP-00102 (Telmisartan) 80mg/5 days + THP-00101 (Dapagliflozin) 10mg/5 days	Drug: THP-00101 (Dapagliflozin) 10mg; Dapagliflozin 10mg Tablet / 5 days in period 1 and period 2 will be given to Arm A Dapagliflozin 10mg Tablet / 5 days in period 2 will be given to Arm B; Other Names: Forxiga Tab. 10mg; Drug: THP-00102 (Telmisartan) 80mg; Telmisartan 80mg Tablet / 5 days in period 1 and period 2 will be given to Arm B Telmisartan 80mg Tablet / 5 days in period 2 will be given to Arm A; Other Names: Micardis Tab. 80mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics - AUCτ,ss	AUCτ,ss of Dapagliflozin & Telmisartan	Day 1 to Day 11
Pharmacokinetics - Cmax,ss	Cmax,ss of Dapagliflozin & Telmisartan	Day 1 to Day 11
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	Evaluate incidents rate of Adverse Event of Treatment-Emergent Adverse Event and compare concomitant medication usage	Day 1 to Day 17

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics - Tmax,ss	Tmax,ss of Dapagliflozin & Telmisartan	Day 1 to Day 11
Pharmacokinetics - Cmin,ss	Cmin,ss of Dapagliflozin & Telmisartan	Day 1 to Day 11
Pharmacokinetics - CLss/F	CLss/F of Dapagliflozin & Telmisartan	Day 1 to Day 11
Pharmacokinetics - Vdss/F	Vdss/F of Dapagliflozin & Telmisartan	Day 1 to Day 11
Pharmacokinetics - PTF	Peak-trough Fluctuation of Dapagliflozin & Telmisartan	Day 1 to Day 11

Collaborators and Investigators

• Sponsor: THPharm Corp.
• Investigators: Principal Investigator: Seung Hyun Kang, M.D, H Plus Yangji Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 9, 2023
• Primary Completion (Actual): November 9, 2023
• Study Completion (Actual): November 9, 2023

Study Registration Dates

• First Submitted: September 8, 2023
• First Submitted That Met QC Criteria: September 25, 2023
• First Posted (Actual): October 2, 2023

Study Record Updates

• Last Update Posted (Estimated): November 22, 2023
• Last Update Submitted That Met QC Criteria: November 20, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Sodium-Glucose Transporter 2 Inhibitors; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Dapagliflozin; Telmisartan
• Other Study ID Numbers: THP-001-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No