Bioequivalence study of three pharmaceutical preparations Atorvastatin tablets.Crossover, randomized, single-dose, three-treatment, three periods and six strings under fasting conditions

• Register: ANZCTR
• Last refreshed on: 13 January 2020
• Main ID: ACTRN12614000851662
• Date of registration: 08/08/2014
• Prospective Registration: No
• Primary sponsor: Ipharma S. A. de C.V.
• Public title: Bioequivalence study of three pharmaceutical preparations Atorvastatin tablets.Crossover, randomized, single-dose, three-treatment, three periods and six strings under fasting conditions
• Scientific title: A bioequivalence study of three pharmaceutical preparations of Atorvastatin tablets, in healthy male volunteers, to test that the pharmaceutical preparations are interchangeable
• Date of first enrolment: 21/01/2011
• Target sample size: 60
• Recruitment status: Completed
• URL: https://anzctr.org.au/ACTRN12614000851662.aspx
• Study type: Interventional
• Study design: Purpose: Treatment; Allocation: Randomised controlled trial; Masking: Blinded (masking used);Assignment: Crossover;Type of endpoint: Bio-equivalence;
• Phase: Phase 1

Countries of recruitment

Mexico

Contacts

• Name: Dr Magdalena Gomez Silva

• Name: Dr Everardo Pineyro Garza

Key inclusion & exclusion criteria

Inclusion criteria: Will be included only those male volunteers who approve the clinical assessment by Ipharma physician’s and pass the clinical biochemistry tests, such as: hematic biometry, blood chemistry, lipid profile and liver function. As well as the absence of any evidence of chronic degenerative disease, and compliant with the following criteria:
-Non-smokers
-18 to 45 years old
- Males
- Body mass index of 20 to 26 Kg/m2
Exclusion criteria: Were excluded from the study those who had electrocardiographic, radiologic abnormalities, which were VDRL (+), HIV (+) and / or HBsAg (+); relatives who had angioedema or allergies to medication, chemically related to drugs and generally any allergies or medical history, as these people have a higher risk of drug allergies. Also lead to exclusion of smoking habits and / or addiction, as well as those who were subject to medical treatment; the existence of concurrent or intercurrent disease and those where there was reasonable doubt about the veracity of the answers in the interview. Finally, all those volunteers who were discordant with the Official Mexican Standard NOM-177-SSA1-1998 were excluded.

Age minimum: 18 Years
Age maximum: 45 Years
Gender: Males

Health Condition(s) or Problem(s) studied

Atorvastatin is an inhibitor of HMG-CoA reductase (statin) indicated as an adjunct therapy to diet to: Reduce the risk of MI and stroke in patients with type 2 diabetes without CHD, but with multiple risk factors. Reduce the risk of non-fatal MI, fatal and non-fatal stroke, revascularization procedures, hospitalization for CHF, and angina in patients with CHD. Reduce elevated total-C, LDL-C, apo B, and TG levels and increase HDL-C in adult patients with primary hyperlipidemia (heterozygous familial and nonfamilial) and mixed dyslipidemia. Reduce elevated TG in patients with hypertriglyceridemia and primary dysbetalipoproteinemia. Reduce total-C and LDL-C in patients with homozygous familial hypercholesterolemia (HoFH). Reduce elevated total-C, LDL-C, and apo B levels in boys and postmenarchal girls, 10 to 17 years of age, with heterozygous familial hypercholesterolemia after failing an adequate trial of diet therapy.;
Atorvastatin is an inhibitor of HMG-CoA reductase (statin) indicated as an adjunct therapy to diet to:
Reduce the risk of MI and stroke in patients with type 2 diabetes without CHD, but with multiple risk factors.

Reduce the risk of non-fatal MI, fatal and non-fatal stroke, revascularization procedures, hospitalization for CHF, and angina in patients with CHD.

Reduce elevated total-C, LDL-C, apo B, and TG levels and increase HDL-C in adult patients with primary hyperlipidemia (heterozygous familial and nonfamilial) and mixed dyslipidemia.

Reduce elevated TG in patients with hypertriglyceridemia and primary dysbetalipoproteinemia.

Reduce total-C and LDL-C in patients with homozygous familial hypercholesterolemia (HoFH).

Reduce elevated total-C, LDL-C, and apo B levels in boys and postmenarchal girls, 10 to 17 years of age, with heterozygous familial hypercholesterolemia after failing an adequate trial of diet therapy.

Metabolic and Endocrine - Normal metabolism and endocrine development and function

Intervention(s)

Test 1: Atorvastatin 80 mg coated tablets.

Test 2: Atorvastatin 80 mg tablets.

Treatment is with a single daily dose of 80 mg of Atorvastatin via oral administration. Three treatments (single dose), 3 periods (one day per period) and two-week washout between each period for the removal of the previous dose.
At least 72 hours before the time fixed for the study, the volunteer will receive in writing the appropriate citation where the place, date and time of the baseline is established. As the following notes for the week before the study: No Smoking (passively, as they are not smokers), not drink alcohol, do not consume xanthine beverages (cola, coffee, tea, chocolate, etc.) not consume grapefruit natural juice, not eating grilled food, do not use any other drug from the week before the study. Each volunteer will be welcomed by doctors and nursing staff involved in the study and they ask about the indications received 72 hours prior. They will be placed in facilities Ipharma SA de CV, will receive a light dinner (less than 800 kcal), low residue. You can drink water until 10:00 PM. Will rise at the time indicated by the staff in the clinical area and take a bath. A member of staff will move to room 1 and 2 as appropriate to randomization.
Each subject will be assigned to three experimental units EU, one for each trial period, so that 01 to 60 is for the period 1 (P1) and 61 to 120 at period 2 (P2) and 121 to 180 for the period 3 (P3).

The staff of each experimental unit consists of nurses, doctors, staff quality area, support staff; as well as the principal investigator.

Each subject will be placed a catheter (Inthracat or equivalent) in the vein of the elbow, they made the decision at time 0 and after this will be administered the d

Primary Outcome(s)

Bioequivalence of the tested drugs (T2 80mg and T3 80mg) compared to reference drug (atorvastatin 80mg tablets, Lipitor registered trademark).

Plasma levels of drugs were measured by high-performance liquid chromatography in an Agilent 1100 tandem mass spectrometry (HPLC) equipped with an auto sampler, a binary pump, connected to detector of triple quadrupole (MS/MS) Agilent 6410 (Agilent Technologies).

Tests to determine bioequivalence: classical confidence interval, interval Westlake, range Shuirmann and Double-sided t test of Shuirmann.[Four weeks post drug administration in the first period.

Timepoint for each period: Thirty-six hours of internment and the blood samples were taken at 0, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 8.0, 12.0, 24.0, 36.0 and 48.0 after drug administration.
]

Secondary Outcome(s)

Absence of late-onset adverse reactions.

Volunteers will be interviewed by the institute doctors about possible side effects of late onset; and Clinical biochemistry tests such as: hematic biometry, blood chemistry, lipid profile and liver function. The information will be recorded in the clinical records.[One week post drug administration in the third period.]

Secondary ID(s)

'Nil known'

Source(s) of Monetary Support

Ipharma S. A. de C.V.

Ethics review

Status: Approved
Approval date:
Contact:

Comite de Etica Ipharma, S. A. de C. V.