Bioequivalence Study of Two Formulations of Telmisartan 80 mg Tablets in Healthy Adult Volunteers Under Fasting State

NCT03705533 | Completed Phase 1

• 1 other identifier: PTL-P3-923
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

This single center, randomized, single dose, full replicate, crossover comparative laboratory-blinded study will be conducted in healthy male and female volunteers in order to determine the bioequivalence of two different formulations of telmisartan 80 mg tablets after oral administration under fasting conditions.

Conditions

Bioequivalence

Keywords

telmisartan; bioequivalence; Micardis

Outcome Measures

Primary Outcomes (2)

• Cmax of telmisartan for the test and the reference products

  Maximum concentration in plasma among observed concentrations at pre-specified time points

  Time points 0.00 (prior to drug administration) and 0.17, 0.33, 0.50, 0.67, 0.83, 1.00, 1.25, 1.50, 2.00, 2.50, 3.00, 4.00, 6.00, 9.00, 12.00, 16.00, 24.00, 36.00, 48.00, 72.00 hours after drug administration

• AUC0-T of telmisartan for the test and the reference products

  Cumulative area under the concentration time curve calculated from 0 to time of last observed quantifiable concentration

  Time points 0.00 (prior to drug administration) and 0.17, 0.33, 0.50, 0.67, 0.83, 1.00, 1.25, 1.50, 2.00, 2.50, 3.00, 4.00, 6.00, 9.00, 12.00, 16.00, 24.00, 36.00, 48.00, 72.00 hours after drug administration

Secondary Outcomes (7)

• Tmax of telmisartan for the test and the reference products

  Time points 0.00 (prior to drug administration) and 0.17, 0.33, 0.50, 0.67, 0.83, 1.00, 1.25, 1.50, 2.00, 2.50, 3.00, 4.00, 6.00, 9.00, 12.00, 16.00, 24.00, 36.00, 48.00, 72.00 hours after drug administration

• TLQC of telmisartan for the test and the reference products

  Time points 0.00 (prior to drug administration) and 0.17, 0.33, 0.50, 0.67, 0.83, 1.00, 1.25, 1.50, 2.00, 2.50, 3.00, 4.00, 6.00, 9.00, 12.00, 16.00, 24.00, 36.00, 48.00, 72.00 hours after drug administration

• AUC0-∞ of telmisartan for the test and the reference products

  Time points 0.00 (prior to drug administration) and 0.17, 0.33, 0.50, 0.67, 0.83, 1.00, 1.25, 1.50, 2.00, 2.50, 3.00, 4.00, 6.00, 9.00, 12.00, 16.00, 24.00, 36.00, 48.00, 72.00 hours after drug administration

• Residual area of telmisartan for the test and the reference products

  Time points 0.00 (prior to drug administration) and 0.17, 0.33, 0.50, 0.67, 0.83, 1.00, 1.25, 1.50, 2.00, 2.50, 3.00, 4.00, 6.00, 9.00, 12.00, 16.00, 24.00, 36.00, 48.00, 72.00 hours after drug administration

• TLIN of telmisartan for the test and the reference products

  Time points 0.00 (prior to drug administration) and 0.17, 0.33, 0.50, 0.67, 0.83, 1.00, 1.25, 1.50, 2.00, 2.50, 3.00, 4.00, 6.00, 9.00, 12.00, 16.00, 24.00, 36.00, 48.00, 72.00 hours after drug administration

Other Outcomes (1)

• Number of treatment-related adverse events (AE) for the test and the reference products

  From the first dosing until 3 days after the collection of the last blood sample of the study

Study Arms (2)

Sequence ABAB

OTHER

Subjects assigned to sequence ABAB will receive a single 80 mg dose of the test product Telmisartan (1 x 80 mg tablet) marked as A in the sequence in Periods 1 and 3 and a single 80 mg dose of the reference product Micardis (1 x 80 mg tablet) marked as B in the sequence in periods 2 and 4. These treatments will be administered orally with approximately 240 mL of water at ambient temperature, in the morning, following a 10-hour overnight fast. The tablet must be swallowed whole and must not be chewed or broken.

Drug: Telmisartan; Drug: Micardis

Sequence BABA

OTHER

Subjects assigned to sequence BABA will receive a single 80 mg dose of the reference product Micardis (1 x 80 mg tablet) marked as B in the sequence in periods 1 and 3 and a single 80 mg dose of the test product Telmisartan (1 x 80 mg tablet) marked as A in the sequence in Periods 2 and 4. These treatments will be administered orally with approximately 240 mL of water at ambient temperature, in the morning, following a 10-hour overnight fast. The tablet must be swallowed whole and must not be chewed or broken.

Drug: Telmisartan; Drug: Micardis

Interventions

Telmisartan DRUG

Telmisartan is manufactured by Pharmtechnology LLC, Belarus. Each tablet contains 80 mg of telmisartan.

Also known as: the test product

Sequence ABAB; Sequence BABA

Micardis DRUG

Micardis is manufactured by Boehringer Ingelheim Ellas AE, Greece. Each tablet contains 80 mg of telmisartan.

Also known as: the reference product

Sequence ABAB; Sequence BABA

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Provision of signed and dated informed consent form (ICF)
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Healthy male or female adult volunteer
• A female volunteer meeting one of the following criteria:
• (1) Physiological postmenopausal status, defined as the following:
• absence of menses for at least one year prior to the first study drug administration (not due to amenorrhea secondary to lactation); and
• Follicle stimulating hormone (FSH) levels ≥ 40 mIU/mL at screening; OR
• (2) Surgical postmenopausal status, defined as the following:
• bilateral oophorectomy; and
• absence of menses for at least 90 days prior to the first study drug administration; and
• FSH levels ≥ 40 mIU/mL at screening; OR
• (3) Hysterectomy with FSH levels ≥ 40 mIU/mL at screening
• Volunteer aged at least 18 years but not older than 55 years
• Volunteer with a body mass index (BMI) within 18.5 kg/m2 to 30.0 kg/m2, inclusively
• Light-, non- or ex-smoker. A light smoker is defined as someone using 10.0 nicotine units or less per day for at least 90 days prior to the first study drug administration. An ex smoker is defined as someone who completely stopped using nicotine products for at least 180 days prior to the first study drug administration

You may not qualify if:

• Females who are pregnant according to the pregnancy test at screening
• Seated blood pressure below 105/60 mmHg at the screening visit or prior to the first study drug administration
• History of significant hypersensitivity to telmisartan or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs
• Presence of significant gastrointestinal, liver or kidney disease, or any other condition known to interfere with drug absorption, distribution, metabolism or excretion, or known to potentiate or predispose to undesired effects
• History of significant gastrointestinal, liver or kidney disease, or surgery that may affect drug bioavailability, including but not limited to cholecystectomy
• History of significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic or dermatologic disease
• Presence of clinically significant ECG abnormalities at the screening visit, as defined by medical judgment
• History of rare hereditary problems of fructose, galactose and/or lactose intolerance, lactase deficiency or glucose-galactose malabsorption
• Maintenance therapy with any drug or significant history of drug dependency or alcohol abuse (\> 3 units of alcohol per day, intake of excessive alcohol, acute or chronic)
• Any clinically significant illness in the 28 days prior to the first study drug administration
• Use of any prescription drugs (with the exception of hormone replacement therapy) in the 28 days prior to the first study drug administration, that in the opinion of an investigator would put into question the status of the volunteer as healthy
• Any history of tuberculosis
• Positive test result for alcohol and/or drugs of abuse at screening or prior to the first drug administration
• Positive screening results to HIV Ag/Ab Combo, Hepatitis B surface Antigen (HBsAG (B) (hepatitis B)) or Hepatitis C Virus (HCV (C)) tests
• Volunteers who have already been included in a previous group for this clinical study

Sponsors & Collaborators

• Pharmtechnology LLC: lead
• Algorithme Pharma, An Altasciences Company: collaborator

Study Sites (1)

Algorithme Pharma, An Altasciences Company

Mount Royal, Quebec, H3P 3P1, Canada

Location

MeSH Terms

Interventions

Telmisartan

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Eric Sicard, MD

  Altasciences Company Inc. (doing business as Algorithme Pharma)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: \*The randomization code will not be available to the personnel of the bioanalytical facility until the bioanalytical tables have been finalized and audited by the Quality Assurance (QA) department. Study participants will be aware they will receive different formulations of the same drug, without being informed which product (Test or Reference) is being administered.
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: In compliance with full replicate design there are two sequences in the study: ABAB and BABA where A = the test product, B = the reference product (see detailed description of items below).

Study Record Dates

• First Submitted: October 8, 2018
• First Posted: October 15, 2018
• Study Start: September 7, 2018
• Primary Completion: December 16, 2018
• Study Completion: December 19, 2018
• Last Updated: December 27, 2018

Record last verified: 2018-12

Locations

CA (1)