A Bioequivalence Study of Two Different Formulations of Olmesartan Medoxomil/ Hydrochlorothiazide After a Single Oral Dose Administration Under Fasting Conditions

NCT04138888 | Unknown Phase 1

• 1 other identifier: PTL-P0-847
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This single dose study was designed in accordance with EMA (the European Medicines Agency) regulatory guidelines, with the aim of characterizing the bioavailability of olmesartan medoxomil/ hydrochlorothiazide in the two formulations (Olmesartan Medoxomil/ Hydrochlorothiazide (HCTZ), 40 mg/ 25 mg film-coated tablets (Manufacturer: Pharmtechnology LLC, Republic of Belarus) and Olmetec Plus® (Olmesartan Medoxomil/ Hydrochlorothiazide), 40 mg/25 mg film-coated tablets, (Manufacturer: Daiichi Sankyo Europe GmbH, Germany)) in healthy subjects. As this is a bioequivalence trial where each subject received each study treatment in a crossover fashion, a control group was not included. Within the clinical portion of the study each subject received a single oral dose of the test and the reference formulation in compliance with the generated randomization code. The primary study endpoints were the pharmacokinetic (PK) parameters Cmax and AUC0-t of olmesartan and hydrochlorothiazide.

Conditions

Bioequivalence

Keywords

Olmesartan medoxomil/hydrochlorothiazide; Bioequivalence; Olmetec Plus®

Outcome Measures

Primary Outcomes (2)

• Cmax of olmesartan and HCTZ 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 0.33, 0.67, 1.00, 1.33, 1.67, 2.00, 2.33, 2.67, 3.00, 3.33, 3.67, 4.00, 4.50, 5.00, 6.00, 8.00, 10.00, 12.00, 24.00, 48.00 hours after each drug administration.

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

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

  Time points 0.00 (prior to each drug administration) and 0.33, 0.67, 1.00, 1.33, 1.67, 2.00, 2.33, 2.67, 3.00, 3.33, 3.67, 4.00, 4.50, 5.00, 6.00, 8.00, 10.00, 12.00, 24.00, 48.00 hours after each drug administration.

Secondary Outcomes (8)

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

  Time points 0.00 (prior to each drug administration) and 0.33, 0.67, 1.00, 1.33, 1.67, 2.00, 2.33, 2.67, 3.00, 3.33, 3.67, 4.00, 4.50, 5.00, 6.00, 8.00, 10.00, 12.00, 24.00, 48.00 hours after each drug administration.

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

  Time points 0.00 (prior to each drug administration) and 0.33, 0.67, 1.00, 1.33, 1.67, 2.00, 2.33, 2.67, 3.00, 3.33, 3.67, 4.00, 4.50, 5.00, 6.00, 8.00, 10.00, 12.00, 24.00, 48.00 hours after each drug administration.

• AUC0-∞ of olmesartan and HCTZ in plasma after administration of the test and the reference products.

  Time points 0.00 (prior to each drug administration) and 0.33, 0.67, 1.00, 1.33, 1.67, 2.00, 2.33, 2.67, 3.00, 3.33, 3.67, 4.00, 4.50, 5.00, 6.00, 8.00, 10.00, 12.00, 24.00, 48.00 hours after each drug administration.

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

  Time points 0.00 (prior to each drug administration) and 0.33, 0.67, 1.00, 1.33, 1.67, 2.00, 2.33, 2.67, 3.00, 3.33, 3.67, 4.00, 4.50, 5.00, 6.00, 8.00, 10.00, 12.00, 24.00, 48.00 hours after each drug administration.

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

  Time points 0.00 (prior to each drug administration) and 0.33, 0.67, 1.00, 1.33, 1.67, 2.00, 2.33, 2.67, 3.00, 3.33, 3.67, 4.00, 4.50, 5.00, 6.00, 8.00, 10.00, 12.00, 24.00, 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/25 mg dose of the test product Olmesartan Medoxomil/ Hydrochlorothiazide (1 x 40 mg/ 25 mg tablet), marked as A in the sequence, in Period 1 and a single 40 mg/25 mg dose of the reference product Olmetec® Plus (1 x 40 mg/ 25 mg tablet), marked as B in the sequence, in period 2. These treatments will be administered orally with approximately 240 mL of water, in the morning, following a 10-hour overnight fast. The tablet must be swallowed whole and must not be chewed or broken.

Drug: Olmesartan Medoxomil/Hydrochlorothiazide 40 Mg/25 Mg film-coated tablets for oral use; Drug: Olmetec® Plus 40 Mg/25 Mg film-coated tablets for oral use

Sequence BA

OTHER

16 subjects assigned to the sequence BA will receive a single 40 mg/25 mg dose of the reference product Olmetec® Plus (1 x 40 mg/ 25 mg tablet), marked as B in the sequence, in Period 1 and a single 40 mg/25 mg dose of the test product Olmesartan Medoxomil/ Hydrochlorothiazide (1 x 40 mg/ 25 mg tablet), marked as A in the sequence, in period 2. These treatments will be administered orally with approximately 240 mL of water, in the morning, following a 10-hour overnight fast. The tablet must be swallowed whole and must not be chewed or broken.

Drug: Olmesartan Medoxomil/Hydrochlorothiazide 40 Mg/25 Mg film-coated tablets for oral use; Drug: Olmetec® Plus 40 Mg/25 Mg film-coated tablets for oral use

Interventions

Olmesartan Medoxomil/Hydrochlorothiazide 40 Mg/25 Mg film-coated tablets for oral use DRUG

Olmesartan Medoxomil/Hydrochlorothiazide is manufactured by Pharmtechnology LLC, Republic of Belarus. Each tablet contains 40 mg of olmesartan medoxomil and 25 mg of hydrochlorothiazide.

Also known as: The test product

Sequence AB; Sequence BA

Olmetec® Plus 40 Mg/25 Mg film-coated tablets for oral use DRUG

Olmetec® Plus is manufactured by Daiichi Sankyo Europe GmbH, Germany. Each tablet contains 40 mg of olmesartan medoxomil and 25 mg of hydrochlorothiazide.

Also known as: The reference product

Sequence AB; Sequence BA

Eligibility Criteria

• Age: 18 Years - 50 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 Caucasian adult male or female;
• If female, meets one of the following criteria:
• A. 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; or
• B. 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
• Aged at least 18 years but not older than 50 years;
• Body mass index (BMI) within 18.50 kg/m2 to 30.00 kg/m2, inclusively;
• Non- or ex smoker (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);
• 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;
• Have no clinically significant (CS) diseases captured in the medical history or evidence of CS findings on the physical examination (including vital signs) and/or electrocardiogram (ECG), as determined by an investigator.

You may not qualify if:

• Female who is lactating at screening;
• Female who is 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 and prior to the first study drug administration;
• Seated blood pressure below 110/60 mmHg at the screening visit and prior to the first study drug administration;
• History of significant hypersensitivity to olmesartan and HCTZ or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs;
• Presence or history of significant gastrointestinal, liver or kidney disease, or any other condition that is known to interfere with drug absorption, distribution, metabolism or excretion, or known to potentiate or predispose to undesired effects;
• History of significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic or dermatologic disease;
• Presence of CS 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 \[1 unit = 10 mL of pure alcohol\], intake of excessive alcohol, acute or chronic);
• Any CS illness in the 28 days prior to the first study drug administration;
• Use of any prescription drugs (with the exception of hormonal contraceptives or 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 participant 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 or hepatitis C virus tests;

Sponsors & Collaborators

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

Study Sites (1)

Altasciences Company Inc.

Mount Royal, Quebec, H3P 3P1, Canada

RECRUITING

MeSH Terms

Interventions

Olmesartan Medoxomil; Hydrochlorothiazide

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles; Chlorothiazide; Benzothiadiazines; Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Thiazides; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Eric Sicard, MD

  Altasciences Company Inc.

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alena Koran

CONTACT

+375293034791; pharmasector@ft.by

Andrei Yaremchuk

CONTACT

+375291268246; 1268246@gmail.com

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

Study Record Dates

• First Submitted: October 23, 2019
• First Posted: October 25, 2019
• Study Start: October 31, 2019
• Primary Completion: December 24, 2019
• Study Completion: December 24, 2019
• Last Updated: December 3, 2019

Record last verified: 2019-10

Locations

CA (1)