Bioequivalence Study of Amlodipine / Losartan/ Hydrochlorothiazide of PHARMALINE, Lebanon Under Fastion Conditions

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.

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.

Study Overview

• Status: Completed
• Conditions: Fasting
• Intervention / Treatment: Drug: Amlodipin, losartan, HCTZ

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 1

Contacts and Locations

Study Locations

• Jordan
  • Amman, Jordan, 1084
    • Pharmaceutical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Healthy subjects.
2. Ethnic Group: Arab & Mediterranean
3. Race: Mixed skin (white & black skin people).
4. Age 18-50 years
5. Body-mass index 18.5 to 30.0 kg/m2 inclusive (minimum of 50 kg weight).
6. Subject is available for the whole study period and gave written informed consent
7. Physical examination within normal ranges
8. All laboratory screening results within the normal range, or being assessed as clinically non-significant by the attending physician
9. Vital signs within normal ranges.
10. Kidney function test, Liver function test should be within normal ranges.
11. Pre dosing blood pressure more than 110/70 mmHg.

Exclusion Criteria:

1. Women of childbearing potential, pregnant and lactating women.
2. Ethnic Group (Non- Arab &/ or Non- Mediterranean)
3. History of severe allergy or allergic reactions to study drug or related drugs or heparin
4. 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
5. History of serious illness that can impact fate of drugs
6. 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
7. Clinically significant illness 4 weeks before study Period I
8. Serious mental disease, drug, alcohol, solvents or caffeine abuse, smoking.
9. Regular use of medication
10. 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
11. Presence of any significant physical or organ abnormality
12. Donation of 1) at least 400 ml of blood within 60 days, or 2) more than 150 ml of blood within 30 days, or 3) more than 100 ml blood plasma or platelets within 14 days before study Period I
13. Participation in another bioequivalence study within 80 days prior to the start of this study Period I
14. Following a special diet (e.g. vegetarian) or dieting one month before the study initiation.
15. Prior history of hypersensitivity to Amlodipine besylate, Losartan Potassium & Hydrochlorothiazide.
16. Consumption of grapefruit or grapefruit containing products within 7 days of drug administration
17. Ingestion of any vitamins or herbal products within 7 days prior to the initial dose of the study medication.
18. Exhausting physical exercise in the last 48 hours (e.g. weight lifting) or any recent significant change in dietary or exercise habits.
19. Any significant clinical abnormality including HBsAg, HCV, and HIV
20. Abnormal vital signs.
21. Abnormal Kidney or Liver function tests.
22. Vomiting, Diarrhea.
23. Pre dosing blood pressure less than 110/70 mmHg
24. Positive test for elicit drugs and alcohol prior to dosing in each period.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: Amlodipin, losartan, HCTZ; Other Names: LOSANET AM PLUS
Active Comparator: 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	Drug: Amlodipin, losartan, HCTZ; Other Names: LOSANET AM PLUS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the bioequivalence of Test oral formulation of LOSANET AM PLUS versus References NORVASC and HYZAAR.	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	9 weeks

Collaborators and Investigators

• Sponsor: Pharmaceutical Research Unit, Jordan
• Investigators: Principal Investigator: Rana .T Bustami, Phd.pharmacy, PRU

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: October 16, 2012
• First Submitted That Met QC Criteria: October 23, 2012
• First Posted (Estimate): October 25, 2012

Study Record Updates

• Last Update Posted (Estimate): July 25, 2013
• Last Update Submitted That Met QC Criteria: July 24, 2013
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: Bio-equivalence, crossover
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Losartan
• Other Study ID Numbers: AMLH423/PRO-00