The Bioequivalence Study of Two Different Formulations of Olmesartan Medoxomil After a Single Oral Dose Administration Under Fasting Conditions.

NCT03951051 | Completed Phase 1

• 1 other identifier: PTL-P1-627 (v. 2.0 05/14/2019)
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This single dose study is designed in accordance with EMA (the European Medicines Agency) regulatory guidelines, with the aim of characterizing the bioavailability of olmesartan in the two formulations in healthy subjects. As this is a bioequivalence trial where each subject will receive each study treatment in a crossover fashion, a control group is not included. Within the clinical portion of the study each subject will receive a single oral dose of the test and the reference formulation in compliance with the generated randomization code. The primary study endpoints are the pharmacokinetic (PK) parameters Cmax and AUC0-t of olmesartan.

Conditions

Bioequivalence

Keywords

Olmesartan Medoxomil; Bioequivalence; Olmetec

Outcome Measures

Primary Outcomes (2)

• Cmax of olmesartan in plasma after administration of the test and the reference products

  Maximum observed concentration in plasma

  Time points 0.00 (prior to each drug administration) and 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.33, 2.67, 3.00, 3.50, 4.00, 5.00, 6.00, 8.00, 12.00, 16.00, 24.00, 36.00, 48.00 hours after each drug administration

• AUC0-t of olmesartan in plasma after administration of the test and the reference products

  Cumulative area under the concentration time curve calculated from 0 to time of last observed quantifiable concentration (TLQC) using the linear trapezoidal method

  Time points 0.00 (prior to each drug administration) and 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.33, 2.67, 3.00, 3.50, 4.00, 5.00, 6.00, 8.00, 12.00, 16.00, 24.00, 36.00, 48.00 hours after each drug administration

Secondary Outcomes (8)

• Tmax of olmesartan in plasma after administration of the test and the reference products

  Time points 0.00 (prior to each drug administration) and 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.33, 2.67, 3.00, 3.50, 4.00, 5.00, 6.00, 8.00, 12.00, 16.00, 24.00, 36.00, 48.00 hours after each drug administration

• TLQC of olmesartan in plasma after administration of the test and the reference products

  Time points 0.00 (prior to each drug administration) and 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.33, 2.67, 3.00, 3.50, 4.00, 5.00, 6.00, 8.00, 12.00, 16.00, 24.00, 36.00, 48.00 hours after each drug administration

• AUC0-INF of olmesartan in plasma after administration of the test and the reference products

  Time points 0.00 (prior to each drug administration) and 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.33, 2.67, 3.00, 3.50, 4.00, 5.00, 6.00, 8.00, 12.00, 16.00, 24.00, 36.00, 48.00 hours after each drug administration

• Residual area of olmesartan in plasma after administration of the test and the reference products

  Time points 0.00 (prior to each drug administration) and 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.33, 2.67, 3.00, 3.50, 4.00, 5.00, 6.00, 8.00, 12.00, 16.00, 24.00, 36.00, 48.00 hours after each drug administration

• Time point where the log-linear elimination phase begins (TLIN) of olmesartan in plasma after administration of the test and the reference products

  Time points 0.00 (prior to each drug administration) and 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.33, 2.67, 3.00, 3.50, 4.00, 5.00, 6.00, 8.00, 12.00, 16.00, 24.00, 36.00, 48.00 hours after each drug administration

Study Arms (2)

Sequence AB

OTHER

16 subjects assigned to the sequence AB will receive a single 40 mg dose of the test product Olmesartan Medoxomil (1 x 40 mg film-coated tablet), marked as A in the sequence, in Period 1 and a single 40 mg dose of the reference product Olmetec® (1 x 40 mg film-coated tablet), marked as B in the sequence, in period 2. These treatments will be administered orally with approximately 240 mL of water at ambient temperature, in the morning, following a minimum of 10-hour overnight fast. The tablet must be swallowed whole and must not be chewed or broken.

Drug: Olmesartan Medoxomil 40 mg; Drug: Olmetec®

Sequence BA

OTHER

16 subjects assigned to the sequence BA will receive a single 40 mg dose of the reference product Olmetec® (1 x 40 mg film-coated tablet), marked as B in the sequence, in Period 1 and a single 40 mg dose of the test product Olmesartan Medoxomil (1 x 40 mg film-coated tablet), marked as A in the sequence, in period 2. These treatments will be administered orally with approximately 240 mL of water at ambient temperature, in the morning, following a minimum of 10-hour overnight fast. The tablet must be swallowed whole and must not be chewed or broken.

Drug: Olmesartan Medoxomil 40 mg; Drug: Olmetec®

Interventions

Olmesartan Medoxomil 40 mg DRUG

Olmesartan Medoxomil is manufactured by Pharmtechnology LLC, Republic of Belarus. Each film-coated tablet contains 40 mg of olmesartan medoxomil.

Also known as: the test product

Sequence AB; Sequence BA

Olmetec® DRUG

Olmetec® is manufactured by Daiichi Sankyo Europe GmbH, Germany. Each film-coated tablet contains 40 mg of olmesartan medoxomil.

Also known as: the reference product

Sequence AB; Sequence BA

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) 2. Stated willingness to comply with all study procedures and availability for the duration of the study 3. Healthy male or female adult volunteer 4. A female volunteer meeting one of the following criteria:
• Physiological postmenopausal status, defined as the following:
• absence of menses for at least one year prior to the first study drug administration (without an alternative medical condition); and
• Follicle stimulating hormone (FSH) levels ≥ 40 mIU/mL at screening;
• 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;
• \. Volunteer aged at least 18 years but not older than 55 years 6. Volunteer with a body mass index (BMI) within 18.5 kg/m2 to 30.0 kg/m2, inclusively 7. 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 8. Clinical laboratory values within the laboratory's stated normal range; if not within this range, they must be without clinical significance, as determined by an investigator 9. Have no clinically significant diseases captured in the medical history or evidence of clinically significant findings on the physical examination (including vital signs) and/or ECG, as determined by an investigator

You may not qualify if:

• Females who are lactating at screening
• Females who are pregnant according to the pregnancy test at screening
• Seated pulse rate less than 50 Beats per Minute (bpm) or more than 100 bpm at the screening visit or prior to the first study drug administration
• Seated blood pressure below 110/60 mmHg at the screening visit or prior to the first study drug administration
• History of significant hypersensitivity to olmesartan 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 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

Sponsors & Collaborators

• Pharmtechnology LLC: lead
• Altasciences Company Inc.: collaborator

Study Sites (1)

Altasciences Company Inc.

Mount Royal, Quebec, H3P 3P1, Canada

Location

MeSH Terms

Interventions

Olmesartan Medoxomil

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles

Study Officials

• Eric Sicard, MD

  Altasciences Company Inc.

  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.
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2019
• First Posted: May 15, 2019
• Study Start: May 6, 2019
• Primary Completion: June 16, 2019
• Study Completion: June 16, 2019
• Last Updated: July 29, 2019

Record last verified: 2019-05

Locations

CA (1)