Nifedipine Bioavailability Study With Oral Single Doses Under Fasting and Fed Conditions
Information source: SocraTec R&D GmbH
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Bioavailability, Therapeutical Indication Not Studied
Intervention: Nifedipine (Gen-nifedipine extended release, previously referred to as Gen-Nifedipine XL) (Drug); Nifedipine (Bayer Healthcare AG manufactured as Adalat® XL®, Adalat® LA, Adalat® Crono, Adalat® OROS) (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: SocraTec R&D GmbH Official(s) and/or principal investigator(s): Frank Donath, MD, Principal Investigator, Affiliation: SocraTec R&D GmbH
Summary
The present study will be performed to investigate and to compare the in-vivo performance of
the two investigational products Gen-nifedipine extended release, (previously referred to as
Gen-Nifedipine XL (Genpharm ULC, Canada)) and Nifedipine(Bayer Healthcare AG manufactured
as Adalat® XL®, Adalat® LA, Adalat® Crono, Adalat® OROS) by comparing their pharmacokinetic
parameters after oral single dose administrations in the fasted and fed state.
Clinical Details
Official title: Randomized, Non-blind, 4-fold Crossover Study on Safety, Tolerability and Pharmacokinetics of Nifedipine After Single Oral Doses of Adalat® LA 60 mg or of a Marketed Generic Version of Nifedipine Retard 60 mg After an Overnight Fasting or Immediately After a High-fat American Breakfast in Healthy Male Volunteers
Study design: Allocation: Randomized, Endpoint Classification: Bio-availability Study, Intervention Model: Crossover Assignment, Masking: Open Label
Primary outcome: PK parameters after s.d. of 60 mg Nifedipine(Bayer Healthcare AG manufactured asAdalat XL,Adalat LA,Adalat Crono,Adalat OROS)and Gen-nifedipine extended release,(previously named as Gen-Nifedipine XL),administered under fasting/fed condition
Secondary outcome: Descriptive characterisation of safety and tolerability of the investigational products in the study population
Detailed description:
In the past, several attempts have been made to develop nifedipine formulations with
pharmacokinetic characteristics similar to the unique characteristics of nifedipine GITS. A
new extended release nifedipine tablet based on an osmotically active system for once a day
administration has been registered under the trade name Gen-nifedipine extended release,
(previously referred to as Gen-Nifedipine XL (Genpharm ULC, Canada)) in Canada.
According to the product monograph of Gen-nifedipine extended release, (previously referred
to as Gen-Nifedipine XL), this tablet consists of a semipermeable membrane surrounding an
osmotically active drug core. After contact with water from the GI tract osmotic pressure in
the core increases, releasing the active drug at a controlled rate through an orifice in the
tablet membrane. The functional principle of this nifedipine tablet seems to be quite
similar to the one of the GITS system.
However, especially in case of modified release formulations, various factors can affect the
absorption and the systemic availability of the drug. Two important factors are i) the drug
release rate from the dosage form and ii) the gastrointestinal transit rate, which in turn
has an influence on the site of absorption. Especially food intake and the caloric content
of a meal can affect drug transit time, luminal dissolution and drug permeability. Thus, the
prandial state may have a significant impact on the in vivo behaviour of such formulations
as a whole and particularly on the drug bioavailability.
For GITS formulations, such as Adalat® XL®, Adalat® LA, Adalat® Crono, Adalat® OROS, earlier
studies have demonstrated that no significant influence of concomitant food-intake occurs.
Eligibility
Minimum age: 18 Years.
Maximum age: 55 Years.
Gender(s): Male.
Criteria:
Inclusion Criteria:
1. sex: male
2. ethnic origin: Caucasian
3. age: 18 - 55 years, inclusive
4. body-mass index (BMI): ³ 22 kg/m² and £ 27 kg/m²
5. good state of health (no clinically significant deviations from normal clinical
results and laboratory findings)
6. the subject must give written informed consent, after having been informed about
benefits and potential risks of the trial, as well as details of the insurance taken
out to cover the subject's participating in the study
Exclusion Criteria:
1. existing cardiac or haematological diseases and/or pathological findings, which might
interfere with the drug's safety, tolerability, absorption and/or pharmacokinetics
2. existing hepatic and/or renal diseases and/or pathological findings, which might
interfere with the drug's safety, tolerability, absorption and/or pharmacokinetics
3. existing gastrointestinal diseases and/or pathological findings, including severe
gastrointestinal or esophageal constriction or narrowing, which might interfere with
the drug's safety, tolerability, absorption and/or pharmacokinetics
4. history of relevant CNS and/or psychiatric disorders and/or currently treated CNS
and/or psychiatric disorders
5. relevant pathological changes in the ECG (12 standard leads) such as a second- or
third-degree AV block, complete bundle branch block, prolongation of the QRS complex
over 120 msec or the QTc-interval above 450 msec
6. known allergic or intolerance reactions to the active ingredient used or to
constituents of the pharmaceutical preparations (e. g. lactose intolerance)
7. subjects with severe allergies or multiple drug allergies
8. systolic blood pressure below 110 mmHg or above 155 mmHg
9. diastolic blood pressure below 60 mmHg or above 95 mmHg
10. resting heart rate in the awake subject below 45 bpm or above 90 bpm
11. laboratory values out of normal range unless the deviation from normal is judged as
not relevant for the study by the investigator
12. positive anti-HIV-test, HBs-AG-test or anti-HCV-test Lack of suitability for the
trial
13. acute or chronic diseases which could affect absorption or metabolism
14. history of or current drug or alcohol dependence
15. regular intake of alcoholic food or beverages of ≥ 40 g pure ethanol per day
16. subjects who are on a diet which could affect the pharmacokinetics of the drug
17. regular intake of caffeine containing food or beverages of ≥ 500 mg (calculated as
caffeine) per day
18. heavy smokers (≥ 10 cigarettes per day or equivalents of other nicotine containing
products)
19. blood donation or other blood loss of more than 400 ml within the last two months
prior to the start of the study
20. participation in a clinical trial during the last two months prior to individual
enrolment of the subject
21. regular treatment with any systemically available medication (except hormonal
replacement therapy e. g. L-thyroxine)
22. subjects, who report a frequent occurrence of migraine attacks Administrative reasons
23. subjects suspected or known not to follow instructions
24. subjects who are unable to understand the written and verbal instructions, in
particular regarding the risks and inconveniences they will be exposed to as a result
of their participation in the study -
Locations and Contacts
SocraTec R&D Probandenstation, Erfurt, Thüringen 99084, Germany
Additional Information
Starting date: April 2009
Last updated: October 20, 2009
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