Comparative, Randomized,, Single Dose, Open-label, Crossover Bioequivalence Study of LOSANET AM PLUS 10mg/100mg/12.5 mg Tablets (One Tablet) of (PHARMALINE, Lebanon) Versus NORVASC 10mg Tablets (One Tablet) of (Pfizer Canada Inc., Kirkland (Quebec)) and HYZAAR 100mg/12.5 Tablets (One Tablet) of (Merck Sharp & Dohme, Quimica de Puerto Rico, Inc, Road 2 Km. 60.3, Sabana Hoyos, Arecibo, PR 00688 for Merck Sharp & Dohme B.V. Haarlem, The Netherlands) in Healthy Subjects Under Fasting Conditions.
Overview
- Phase
- Phase 1
- Intervention
- Amlodipin, losartan, HCTZ
- Conditions
- Fasting
- Sponsor
- Pharmaceutical Research Unit, Jordan
- Enrollment
- 39
- Locations
- 1
- Primary Endpoint
- To assess the bioequivalence of Test oral formulation of LOSANET AM PLUS versus References NORVASC and HYZAAR.
- Status
- Completed
- Last Updated
- 12 years ago
Overview
Brief Summary
To assess the bioequivalence of the investigational TEST product with the marketed REFERENCE products by measurement of Plasma concentrations of Amlodipine ,Losartan, Carboxylic acid losartan metabolite & Hydrochlorothiazide in plasma and calculation of the bioequivalence parameters from those measurements followed by ANOVA and 90% confidence interval statistical evaluation.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy subjects.
- •Ethnic Group: Arab \& Mediterranean
- •Race: Mixed skin (white \& black skin people).
- •Age 18-50 years
- •Body-mass index 18.5 to 30.0 kg/m2 inclusive (minimum of 50 kg weight).
- •Subject is available for the whole study period and gave written informed consent
- •Physical examination within normal ranges
- •All laboratory screening results within the normal range, or being assessed as clinically non-significant by the attending physician
- •Vital signs within normal ranges.
- •Kidney function test, Liver function test should be within normal ranges.
Exclusion Criteria
- •Women of childbearing potential, pregnant and lactating women.
- •Ethnic Group (Non- Arab \&/ or Non- Mediterranean)
- •History of severe allergy or allergic reactions to study drug or related drugs or heparin
- •Known history or presence of food allergies, or any surgical or medical condition known to interfere with the absorption, distribution, metabolism or excretion of drugs
- •History of serious illness that can impact fate of drugs
- •Known history or presence of cardiac, pulmonary, gastrointestinal, endocrine, musculoskeletal, neurological, hematological, liver or kidney disease, unless judged not clinically significant by the Principal Investigator, or medical designate
- •Clinically significant illness 4 weeks before study Period I
- •Serious mental disease, drug, alcohol, solvents or caffeine abuse, smoking.
- •Regular use of medication
- •Having taken medication that could affect the investigated drug product: a) Regular consumption of drugs during the two weeks prior to study initiation day, b) consumption of enzyme stimulating or inhibiting drugs (e.g. Barbiturates, Carbamazepine, Phenytoin, Amphetamine, benzodiazepine, cannabinoid, cocaine, opiates, phencyclidine, and methadone) during one month before the study initiation
Arms & Interventions
LOSANET AM PLUS (10/100/12.5 mg) of PHARMALINE, Lebanon
Subjects will be fasted overnight and receive one tablet by mouth in accordance with randomization table, and blood samples will be taken at specified intervals over 3 days intervention: Drug: LOSANET AM PLUS Amlodipine/ Losartan/Hydrochlorothiazide Other Name: NA
Intervention: Amlodipin, losartan, HCTZ
NORVASC & HYZAAR (100/12.5 mg)
Subjects will be fasted overnight and receive one tablet of Norvasc \&HYZAAR by mouth in accordance with randomization table, and blood samples will be taken over 3 days intervention: Drug: LOSANET AM PLUS Amlodipine/ Losartan/Hydrochlorothiazide Other Name: NA
Intervention: Amlodipin, losartan, HCTZ
Outcomes
Primary Outcomes
To assess the bioequivalence of Test oral formulation of LOSANET AM PLUS versus References NORVASC and HYZAAR.
Time Frame: 9 weeks
To assess the bioequivalence of the investigational TEST product with the marketed REFERENCE products by measurement of Plasma concentrations of Amlodipine ,Losartan, Carboxylic acid losartan metabolite \& Hydrochlorothiazide in plasma and calculation of the bioequivalence parameters from those measurements followed by ANOVA and 90% confidence interval statistical evaluation. Cmax Ratio: Scaled average bioequivalence will be performed. Bioequivalence limits will be defined and widened according to the variance of σw2 within subject variability for the reference based on Amlodipine, Losartan, \& Hydrochlorothiazide AUC Ratio: The 90% confidence interval for this measure lies within an acceptance range of 80.00% - 125.00% based on Losartan, \& Hydrochlorothiazide AUC0-72 Ratio: The 90% confidence interval for this measure lies within an acceptance range of 80.00 - 125.00 % based on Amlodipine Carboxylic acid Losartan metabolite will be considered as supportive data