Evaluation of Individual Bioequivalence of Gabasandoz® Relative to Neurontin® in Healthy Volunteers

Epilepsy and Neuropathic Pain Clinical Trial

— DRUG13-GABA  

Official title:

A Single Centre, Single-blind, Randomized, Two-part, 6-way Cross-over Study to Investigate the Individual Bioequivalence of Gabasandoz® Relative to Neurontin® in Healthy Volunteers.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01821235
• Other study ID #: EC/2013/210
• Secondary ID: 2013-001157-27
• Status: Completed
• Phase: Phase 1
• First received: March 26, 2013
• Last updated: January 28, 2014
• Start date: April 2013
• Est. completion date: November 2013

Study information

• Verified date: January 2014
• Source: University Hospital, Ghent
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

The NO SWITCH list is based on the hypothesis that the pharmacokinetic differences between different batches of one medicines are smaller than the pharmacokinetic differences between two medicines (from a different manufacturer, e.g. brand versus generic medicine). The aim of this study is to investigate the hypothesis using gabapentin as test product. Therefore, the first objective of this study is to investigate the individual bioequivalence - or switchability - of Gabasandoz® 800 mg relative to Neurontin 800 mg®. The second objective is to investigate the individual bioequivalence between two different batches of the same medicine, for Gabasandoz® 800 mg and Neurontin® 800 mg.

Description:

At the end of 2011, the Belgian Federal Agency for Medicines and Health Products (FAMHP) introduced a list of medicines, called the 'NO SWITCH' list1. This list contains 42 active pharmaceutical ingredients with a narrow therapeutic index (i.e. small differences between the effective and toxic concentration), very toxic ingredients and all antiepileptics. For the active ingredients on the NO SWITCH-list, the FAMHP advises, once treatment is started with a medicines from a particular manufacturer, to continue treatment with exactly the same medicine (from the same manufacturer). In other words, switching from e.g. Neurontin® 800 mg to Gabasandoz® 800 mg during treatment is not recommended. However, switching is possible, but only when done carefully and under the supervision of a physician.

The NO SWITCH list is based on the hypothesis that the pharmacokinetic differences between different batches of one medicines are smaller than the pharmacokinetic differences between two medicines (from a different manufacturer, e.g. brand versus generic medicine).

The aim of this study is to investigate the hypothesis using gabapentin as test product. Therefore, the first objective of this study is to investigate the individual bioequivalence

• or switchability - of Gabasandoz® 800 mg relative to Neurontin 800 mg®. The second objective is to investigate the individual bioequivalence between two different batches of the same medicine, for Gabasandoz® 800 mg and Neurontin® 800 mg.

This is a two-parted study. The first part is a 6 way crossover pilot study with 12 healthy volunteers (men and women). Data from this pilot study will be used to determine the following pharmacokinetic parameters: AUC0-t, AUC, Cmax and T1/2. The obtained data will be used to develop a Limited Sampling Strategy (LSS), i.e. a strategy to determine AUC and Cmax from a limited number of plasma concentrations. A simulation study will be performed, using data from the pilot study to determine the amount of volunteers needed to result into an appropriate statistical power. This simulation study will be performed according to the FDA Guidance for Industry: Statistical Approaches to Establishing Bioequivalence2.

Part two of the study will be a 6 way crossover and AUC and Cmax will be determined using the developed Limited Sampled Strategy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 51
• Est. completion date: November 2013
• Est. primary completion date: November 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Healthy males and females aged between 18 and 55 years at screening, extremes included.

• A Body Mass Index of 18.0 to 30.0 kg/m².

• Good physical and mental health.

• Subject is a non-smoker for at least 3 months prior to dosing.

Exclusion Criteria:

• Clinically relevant abnormal laboratory, ECG recordings, vital signs or physical findings at screening as judged by the investigator.

• History of hypersensitivity or idiosyncrasy to gabapentin or any other anti-convulsive agents.

• Positive serology for hepatitis B antigen, hepatitis C antibodies, HIV 1 or HIV 2 antibodies.

• History of alcohol or drug abuse within the last 2 years.

• Blood donation within 1 month before screening.

• Female subjects who are pregnant or lactating.

Study Design

Allocation: Randomized, Endpoint Classification: Bio-equivalence Study, Intervention Model: Crossover Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Epilepsy and Neuropathic Pain
• Neuralgia

Intervention

Drug:
• Neurontin® (gabapentin) batch A
Neurontin® 800 mg tablets (gabapentin) batch A, given 2 times
• Neurontin® (gabapentin) batch B
Neurontin® 800 mg tablets (gabapentin) batch B, given 1 time
• Gabasandoz® (gabapentin) batch A
Gabasandoz® 800 mg tablets (gabapentin) batch A, given 2 times
• Gabasandoz® (gabapentin) batch B
Gabasandoz® 800 mg tablets (gabapentin) batch A, given 1 time

Locations

Country	Name	City	State
Belgium	Drug Research Unit Ghent (D.R.U.G.)	Ghent

Sponsors (3)

Lead Sponsor	Collaborator
University Hospital, Ghent	University Ghent, VU University Medical Center

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area under the plasma concentration versus time curve (AUC) and Peak Plasma Concentration (Cmax) of Neurontin® 800 mg	16 bloodsamples will be taken; Blood samples taken at 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 4.5h, 5h, 6h, 7h, 8h, 10h, 12h, 24h, 36h post-dose.	As of from dosing till 36 h postdose	No
Primary	Area under the plasma concentration versus time curve (AUC) and Peak Plasma Concentration (Cmax) of Gabasandoz® 800 mg	16 bloodsamples will be taken; Blood samples taken at 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 4.5h, 5h, 6h, 7h, 8h, 10h, 12h, 24h, 36h post-dose.	As of from dosing till 36 h postdose	No