BioequivalencePhase 1NCT03951051
The Bioequivalence Study of Two Different Formulations of Olmesartan Medoxomil After a Single Oral Dose Administration Under Fasting Conditions.
A Phase 1 study testing Olmesartan Medoxomil 40 mg and Olmetec® in people with Bioequivalence, run by Pharmtechnology LLC at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Bioequivalence
- What is being tested?
- Olmesartan Medoxomil 40 mg and Olmetec®
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteCanada
- Study dates
- 6 May 2019to 16 Jun 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 1. 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;
- or
- Surgical postmenopausal status, defined as the following:
Show all 12Show fewer
- 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
- Hysterectomy with FSH levels ≥ 40 mIU/mL at screening If the postmenopausal volunteer has an FSH of < 40 mIU/mL, but meets the above criteria in either (1), (2) or (3) and all the other inclusion criteria, the volunteer may be included in the study if the estradiol serum level measured at screening is equal to or below 150 pmol/L. In the case of hysterectomy, if FSH and estradiol do not meet the criteria, inclusion of the volunteer will be based on medical judgment.
- 5. 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
Who cannot join
- 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
Show all 21Show fewer
- 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
- Positive screening results to HIV Ag/Ab Combo, Hepatitis B surface Antigen or Hepatitis C Virus tests
- Volunteers who have already been included in a previous group for this clinical study
- Volunteers who took olmesartan in the 28 days prior to the first study drug administration
- Volunteers who took an Investigational Product (IP) in the 28 days prior to the first study drug administration
- Volunteers who donated 50 mL or more of blood in the 28 days prior to the first study drug administration
- Donation of 500 mL or more of blood (Canadian Blood Services, Hema-Quebec, clinical studies, etc.) in the 56 days prior to the first study drug administration
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Single Dose Crossover Comparative Bioavailability Study of Olmesartan Medoxomil 40 mg Film-coated Tablets in Healthy Adult Subjects Under Fasting Conditions.
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.
Read the detailed description
This is a single center, randomized, 2-treatment, 2-period, 2-sequence, crossover, single dose study design, in which 32 healthy adult subjects will receive one of the study treatments during each study period.
The objective of this study is to determine the bioequivalence of two different formulations of olmesartan after a single oral dose administration under fasting conditions.
The intra-subject variation following a single dose of olmesartan appears to be around 25% for Cmax and around 18% for AUC0-t. Statistically, given that the expected Test to Reference ratio of geometric least-squares means (LSmeans) should fall within 95 and 105%, it is estimated that the lowest number of subjects to meet the 80 to 125% bioequivalence range with a statistical a priori power of at least 80% is about 28. Therefore, the inclusion of 32 subjects should be sufficient to account for the possibility of drop-outs, variations around the estimated intra-subject coefficient of variation (CV) and to conclude in favor of the hypothesis of bioequivalence with sufficient statistical power.
Subject eligibility for this study will be determined at the screening visit and eligible subjects will be admitted to the clinical research unit at least 10 hours prior to drug administration for each study period.
A subject who withdraws or is withdrawn during the pretrial evaluations but before receiving the first dose (the test or the reference product) in Period 1 will not be considered as a drop-out and will not be included in the final database. Standbys should be recruited and available to replace any subject who withdraws prior to the first drug administration. On-study drop-outs will not be replaced.
Altasciences will generate the randomization code with a computer program according to the study design, the number of subjects and the sequence of treatment administration. The random allocation of each sequence of treatment administration to each subject will be done in such a way that the study is balanced. Once generated, the randomization code will be final and will not be modified. Eligible subjects will be randomized to one of two treatment sequences. There will be two sequences in the study: AB and BA, where A = the test product, B = the reference product (see detailed description of A and B items in Section "Arms and Interventions").
For each study period, subjects will receive a single 40 mg oral dose of olmesartan medoxomil (the test or the reference formulation). 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.The date and time of each dose will be recorded. For each subject, all scheduled postdose activities and assessments will be performed relative to the time of study drug administration.
Fasting will continue for at least 4 hours following drug administration, after which a standardized lunch will be served. A supper and a light snack will be served at appropriate times thereafter, but not before 9 hours after dosing. Water will be provided as needed until 1 hour predose. Water will be allowed beginning 1 hour after the administration of the drug.
A total of 21 blood samples will be collected (one tube of 3 mL each) in each study period for pharmacokinetic (PK) assessments.The first blood sample will be collected prior to drug administration while the others will be collected up to 48 hours after drug administration.
Given that the parent compound, olmesartan medoxomil, is rapidly and completely converted to the pharmacologically active metabolite, olmesartan, and that no intact olmesartan medoxomil or intact side chain medoxomil moiety have been detected in plasma, olmesartan medoxomil cannot be reliably measured. Therefore, the analyte to be measured in the present study will be olmesartan. Olmesartan plasma concentrations will be measured according to a validated bioanalytical method.
Subjects are to be discharged from the clinic after the 24-hour postdose PK sample collection, and following medical approval. However, they may be advised to stay at the clinical site for safety reasons, if judged necessary by the physician in charge. Subjects will return to the clinic for blood collections at 36 and 48 hours postdose.
The expected terminal elimination half-life observed after a single oral 40 mg dose of olmesartan medoxomil tablets under fasting conditions is 9.4 hours. To avoid any carry-over effect, a wash-out of 7 calendar days is planned between drug administrations.
The decision of which subjects will be included in the PK analysis is to be documented by the pharmacokineticist (or delegate) and approved by the sponsor before the start of the sampleanalysis by the bioanalytical facility. Subjects who are expected to provide evaluable PK data for both the Test and Reference products (based on viable PK samples) will be included in the PK analysis. Concentration data of the remaining subjects will be presented separately. Subjects who do not complete the sampling schedule of one or more study periods may be included in the PK and statistical analysis and bioequivalence determination for only the PK parameters that are judged not to be affected by the missing sample(s).
Statistical analysis of Tmax will be based on a non-parametric approach. Statistical analysis of all other PK parameters will be based on an Analysis of Variance (ANOVA) model. Two-sided 90% confidence interval of the ratio of geometric LSmeans obtained from the ln-transformed PK parameters will be calculated.
Statistical inference of olmesartan will be based on a bioequivalence approach using the following standards: the ratio of geometric LSmeans with corresponding 90% confidence interval calculated from the exponential of the difference between the Test and the Reference for the ln-transformed parameters Cmax and AUC0-t should all be within the 80.00 to 125.00% bioequivalence range.
The safety population will include all subjects who received at least one formulation (Test or Reference). Safety assessments will include vital signs, clinical laboratory tests and AE monitoring. Additional safety measurements may be performed at the discretion of the investigator for reasons related to subject safety.The physician in charge will be present at the clinical site for at least the first 4 hours following each drug administration and will remain available at all times throughout the study.
Total study duration: up to 32 days (including screening).
- Conditions
- Bioequivalence
- Being tested
- Olmesartan Medoxomil 40 mg, Olmetec®
- Keywords
- Olmesartan Medoxomil, Bioequivalence, Olmetec
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Olmesartan Medoxomil 40 mgDrug
Also called the test product
Olmesartan Medoxomil is manufactured by Pharmtechnology LLC, Republic of Belarus. Each film-coated tablet contains 40 mg of olmesartan medoxomil.
Olmetec®Drug
Also called the reference product
Olmetec® is manufactured by Daiichi Sankyo Europe GmbH, Germany. Each film-coated tablet contains 40 mg of olmesartan medoxomil.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Olmesartan Medoxomil 40 mg; Drug: Olmetec® |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cmax of olmesartan in plasma after administration of the test and the reference products
Maximum observed concentration in plasma
Measured: 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
Measured: 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 of maximum observed concentration; if it occurs at more than one time point, Tmax is defined as the first time point with this value
Measured: 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 of last observed quantifiable concentration
Measured: 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
Area under the concentration time curve extrapolated to infinity, calculated as AUC0-t + ĈLQC (the predicted concentration at time TLQC) / λZ (apparent elimination rate constant)
Measured: 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
Extrapolated area (i.e. percentage of AUC0-INF due to extrapolation from TLQC to infinity)
Measured: 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 point where the log-linear elimination phase begins
Measured: 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
λZ of olmesartan in plasma after administration of the test and the reference products
Apparent elimination rate constant, estimated by linear regression of the terminal linear portion of the log concentration versus time curve
Measured: 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
Terminal elimination half-life (Thalf) of olmesartan in plasma after administration of the test and the reference products
Terminal elimination half-life, calculated as ln(2)/λZ
Measured: 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
Number of treatment-emergent adverse events for the test and the reference products
The safety population will include all subjects who received at least one dose of the test or the reference product. Any significant changes will be recorded as treatment-emergent adverse events only if they are judged clinically significant by the qualified investigator or delegate.
Measured: Up to 10 days (after the first drug administration until the completion of clinical part of the study)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2019
- Study start6 May 2019
- Primary completion16 Jun 2019
- Study completion16 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for BioequivalenceStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pharmtechnology LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Altasciences Company Inc.
- Responsible party
- Sponsor
- Investigators
- Eric Sicard, MD, Principal investigator, Altasciences Company Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03951051
- Sponsor's protocol ID
- PTL-P1-627 (v. 2.0 05/14/2019)
- Status last verified
- May 2019
- First submitted
- 13 May 2019
- Last updated
- 29 Jul 2019
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single Dose Crossover Comparative Bioavailability Study of Olmesartan Medoxomil 40 mg Film-coated Tablets in Healthy Adult Subjects Under Fasting Conditions.
- ClinicalTrials.gov ID
- NCT03951051
- Acronym / sponsor ID
- PTL-P1-627 (v. 2.0 05/14/2019)
- Conditions
- Bioequivalence
- Keywords
- Olmesartan Medoxomil, Bioequivalence, Olmetec
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Pharmtechnology LLCIndustry (pharma, biotech, devices)
- Collaborators
- Altasciences Company Inc.
- Study start
- 6 May 2019 (actual)
- Primary completion
- 16 Jun 2019 (actual)
- Study completion
- 16 Jun 2019 (actual)
- First posted
- 15 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a single center, randomized, 2-treatment, 2-period, 2-sequence, crossover, single dose study design, in which 32 healthy adult subjects will receive one of the study treatments during each study period.
The objective of this study is to determine the bioequivalence of two different formulations of olmesartan after a single oral dose administration under fasting conditions.
The intra-subject variation following a single dose of olmesartan appears to be around 25% for Cmax and around 18% for AUC0-t. Statistically, given that the expected Test to Reference ratio of geometric least-squares means (LSmeans) should fall within 95 and 105%, it is estimated that the lowest number of subjects to meet the 80 to 125% bioequivalence range with a statistical a priori power of at least 80% is about 28. Therefore, the inclusion of 32 subjects should be sufficient to account for the possibility of drop-outs, variations around the estimated intra-subject coefficient of variation (CV) and to conclude in favor of the hypothesis of bioequivalence with sufficient statistical power.
Subject eligibility for this study will be determined at the screening visit and eligible subjects will be admitted to the clinical research unit at least 10 hours prior to drug administration for each study period.
A subject who withdraws or is withdrawn during the pretrial evaluations but before receiving the first dose (the test or the reference product) in Period 1 will not be considered as a drop-out and will not be included in the final database. Standbys should be recruited and available to replace any subject who withdraws prior to the first drug administration. On-study drop-outs will not be replaced.
Altasciences will generate the randomization code with a computer program according to the study design, the number of subjects and the sequence of treatment administration. The random allocation of each sequence of treatment administration to each subject will be done in such a way that the study is balanced. Once generated, the randomization code will be final and will not be modified. Eligible subjects will be randomized to one of two treatment sequences. There will be two sequences in the study: AB and BA, where A = the test product, B = the reference product (see detailed description of A and B items in Section "Arms and Interventions").
For each study period, subjects will receive a single 40 mg oral dose of olmesartan medoxomil (the test or the reference formulation). 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.The date and time of each dose will be recorded. For each subject, all scheduled postdose activities and assessments will be performed relative to the time of study drug administration.
Fasting will continue for at least 4 hours following drug administration, after which a standardized lunch will be served. A supper and a light snack will be served at appropriate times thereafter, but not before 9 hours after dosing. Water will be provided as needed until 1 hour predose. Water will be allowed beginning 1 hour after the administration of the drug.
A total of 21 blood samples will be collected (one tube of 3 mL each) in each study period for pharmacokinetic (PK) assessments.The first blood sample will be collected prior to drug administration while the others will be collected up to 48 hours after drug administration.
Given that the parent compound, olmesartan medoxomil, is rapidly and completely converted to the pharmacologically active metabolite, olmesartan, and that no intact olmesartan medoxomil or intact side chain medoxomil moiety have been detected in plasma, olmesartan medoxomil cannot be reliably measured. Therefore, the analyte to be measured in the present study will be olmesartan. Olmesartan plasma concentrations will be measured according to a validated bioanalytical method.
Subjects are to be discharged from the clinic after the 24-hour postdose PK sample collection, and following medical approval. However, they may be advised to stay at the clinical site for safety reasons, if judged necessary by the physician in charge. Subjects will return to the clinic for blood collections at 36 and 48 hours postdose.
The expected terminal elimination half-life observed after a single oral 40 mg dose of olmesartan medoxomil tablets under fasting conditions is 9.4 hours. To avoid any carry-over effect, a wash-out of 7 calendar days is planned between drug administrations.
The decision of which subjects will be included in the PK analysis is to be documented by the pharmacokineticist (or delegate) and approved by the sponsor before the start of the sampleanalysis by the bioanalytical facility. Subjects who are expected to provide evaluable PK data for both the Test and Reference products (based on viable PK samples) will be included in the PK analysis. Concentration data of the remaining subjects will be presented separately. Subjects who do not complete the sampling schedule of one or more study periods may be included in the PK and statistical analysis and bioequivalence determination for only the PK parameters that are judged not to be affected by the missing sample(s).
Statistical analysis of Tmax will be based on a non-parametric approach. Statistical analysis of all other PK parameters will be based on an Analysis of Variance (ANOVA) model. Two-sided 90% confidence interval of the ratio of geometric LSmeans obtained from the ln-transformed PK parameters will be calculated.
Statistical inference of olmesartan will be based on a bioequivalence approach using the following standards: the ratio of geometric LSmeans with corresponding 90% confidence interval calculated from the exponential of the difference between the Test and the Reference for the ln-transformed parameters Cmax and AUC0-t should all be within the 80.00 to 125.00% bioequivalence range.
The safety population will include all subjects who received at least one formulation (Test or Reference). Safety assessments will include vital signs, clinical laboratory tests and AE monitoring. Additional safety measurements may be performed at the discretion of the investigator for reasons related to subject safety.The physician in charge will be present at the clinical site for at least the first 4 hours following each drug administration and will remain available at all times throughout the study.
Total study duration: up to 32 days (including screening).
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sequence AB | Other | Drug: Olmesartan Medoxomil 40 mg, Drug: Olmetec®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. |
| Sequence BA | Other | Drug: Olmesartan Medoxomil 40 mg, Drug: Olmetec®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. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (12 listed)
- 1. 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:
- or
- Surgical postmenopausal status, defined as the following:
- or
Key exclusion criteria (21 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Olmesartan Medoxomil 40 mgAlso: the test productOlmesartan Medoxomil is manufactured by Pharmtechnology LLC, Republic of Belarus. Each film-coated tablet contains 40 mg of olmesartan medoxomil. | Drug | Sequence AB, Sequence BA |
| Olmetec®Also: the reference productOlmetec® is manufactured by Daiichi Sankyo Europe GmbH, Germany. Each film-coated tablet contains 40 mg of olmesartan medoxomil. | Drug | Sequence AB, Sequence BA |
Primary outcome
Cmax of olmesartan in plasma after administration of the test and the reference products
Time frame: 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
Maximum observed concentration in plasma
AUC0-t of olmesartan in plasma after administration of the test and the reference products
Time frame: 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
Cumulative area under the concentration time curve calculated from 0 to time of last observed quantifiable concentration (TLQC) using the linear trapezoidal method
8 secondary outcomes
Tmax of olmesartan in plasma after administration of the test and the reference products
Time frame: 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 frame: 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 frame: 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 frame: 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 frame: 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
λZ of olmesartan in plasma after administration of the test and the reference products
Time frame: 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
Terminal elimination half-life (Thalf) of olmesartan in plasma after administration of the test and the reference products
Time frame: 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
Number of treatment-emergent adverse events for the test and the reference products
Time frame: Up to 10 days (after the first drug administration until the completion of clinical part of the study)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jul 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eric Sicard, MD principal investigator
Altasciences Company Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Olmesartan Medoxomil 40 mg and Olmetec® in people with Bioequivalence, run by Pharmtechnology LLC at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cmax of olmesartan in plasma after administration of the test and the reference products (time frame: 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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jul 2019.