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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pharmaceutical Research Unit, Jordan
ClinicalTrials.gov Identifier:
NCT01713647
First received: October 16, 2012
Last updated: July 24, 2013
Last verified: October 2012
  Purpose

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.


Condition Intervention Phase
Fasting
Drug: Amlodipin, losartan, HCTZ
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by Pharmaceutical Research Unit, Jordan:

Primary Outcome Measures:
  • To assess the bioequivalence of Test oral formulation of LOSANET AM PLUS versus References NORVASC and HYZAAR. [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]

    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



Enrollment: 39
Study Start Date: October 2012
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: LOSANET AM PLUS

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01713647

Locations
Jordan
Pharmaceutical research unit
Amman, Jordan, 1084
Sponsors and Collaborators
Pharmaceutical Research Unit, Jordan
Investigators
Principal Investigator: Rana .T Bustami, Phd.pharmacy PRU
  More Information

No publications provided

Responsible Party: Pharmaceutical Research Unit, Jordan
ClinicalTrials.gov Identifier: NCT01713647     History of Changes
Other Study ID Numbers: AMLH423/PRO-00
Study First Received: October 16, 2012
Last Updated: July 24, 2013
Health Authority: Jordan: Jordan food and drug administation

Keywords provided by Pharmaceutical Research Unit, Jordan:
Bio-equivalence, crossover

Additional relevant MeSH terms:
Hydrochlorothiazide
Amlodipine
Losartan
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Sodium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Calcium Channel Blockers
Vasodilator Agents
Anti-Arrhythmia Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists

ClinicalTrials.gov processed this record on July 22, 2014