The aim of this study is to investigate the possible consequences of generic-generic substitution of gabapentin, a frequently used anti-epileptic drug.
ID
Source
Brief title
Condition
- Other condition
- Peripheral neuropathies
Synonym
Health condition
epilepsie
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To compare the pharmacokinetic profile of gabapentin from the Neurontin® 800 mg
tablet and three generic gabapentin 800 mg tablets after single dose
administration of 800 mg in healthy volunteers under fasting conditions.
The main endpoints will be the 90% confidence intervals of the ratio of
least-squares means of the pharmacokinetic parameters AUC0-t, AUCinf, and Cmax
of two tested gabapentin products (for all combinations among the four
products).
Secondary outcome
To compare the tolerability and safety of gabapentin from the Neurontin® 800 mg
tablet and three generic gabapentin 800 mg tablets after single dose
administration of 800 mg in healthy volunteers under fasting conditions.
Background summary
In clinical practice, generic drugs (generics) are often interchanged, whereas
factual data regarding generic-generic interchangeability are lacking. Under
these conditions, the so-called *shift* or *drift* problem that may occur when
generics are interchanged may be reason for concern; while generics are
exchangeable with the innovator product, generics themselves may not be, which
may lead to loss of efficacy or increased toxicity. This problem may be
relevant for certain drugs with a narrow therapeutic window, including
anti-epileptic drugs, where seizure control may be lost or side-effects may
increase when patients switch from one generic to another.
Study objective
The aim of this study is to investigate the possible consequences of
generic-generic substitution of gabapentin, a frequently used anti-epileptic
drug.
Study design
Randomized, four-period, four-treatment, crossover, balanced, single dose
comparative oral bioavailability study in healthy, adult, subjects under
fasting conditions.
Intervention
There will be 4 periods of administration of gabapentin, each separated by one
week. Each volunteer will receive a single dose of 800 mg of gabapentin after
an overnight fast (either Neurontin® or one of the 3 generic gabapentin tablets
in a randomized order) at the beginning of each period, i.e., on Day 1, Day 8,
Day 15, or Day 22.
Study burden and risks
Study participants will undergo a medical history taking, physical examination
(2 times), routine laboratory blood (6 times) and urine tests (2 times), urine
pregnancy tests (5 times, females only), urine testing for recreational drugs
(5 times), alcohol breath tests (5 times), a 12-lead ECG (2 times) and
measurements of vital signs, i.e. heart rate, blood pressure, temperature and
respiratory rate (38 times) and venous blood sampling for analysis of
gabapentin plasma concentration (12 times by venapunction, 56 times by
peripheral venous catheter). A total of 306 mL of blood will be sampled from
each participant during the study. A repeated blood or urine sampling may be
performed when deemed necessary to check or follow up an abnormal result from a
previous sample.
After a screening visit, each participant will visit the trial centre 4 times
for a night (from 22 pm) and day (till 12 hours after dosing), and will fast
for at least 10 hours before dosing until 4 hours post-dose. Water will be
restricted for one hour before and after dosing.
Gabapentin has been demonstrated to be safe in humans within the effective
dosing range from 900 to 3600 mg/day. Participants will not benefit directly
from participation.
P. Debyelaan 25
6229 HX Maastricht
NL
P. Debyelaan 25
6229 HX Maastricht
NL
Listed location countries
Age
Inclusion criteria
*male or female volunteer, 18-55 years of age;
*non-smoking (for at least 3 months) or moderately smoking, i.e. less than 10 cigarettes a day;
*weighing in the normal range according to accepted normal values of BMI Chart (18-30kg/m2);
*in a healthy condition, as assessed bij the investigator based on medical history, physical exam, vital signs, routine laboratiry tests and 12-lead ECG;
*females of childbearing potential should either be sexual inactive for 14 days prior to the first dose and throughout the study or be using an acceptable birth control method;
*voluntary consenting to participate in the study.
Exclusion criteria
*history or presence of significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or psychiatric disease;
*a positive test result for HIV, hepatitis B and C;
*history or presence of alcoholism or drug abuse within the past year or hypersensitivity or idiosyncratic reaction to gabapentin or any other anticonvulsive agents;
*female subjects who are pregnant or lactating;
*subjects who have a variable, instable nutrition pattern;
*subjects who have donated blood within the last 2 months, or who have donated plasma within the last 14 days;
*subjects who have participated in another clinical trial within 28 days prior to start to the first dose.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2011-002335-26-NL |
| CCMO | NL37405.056.11 |