We updated the design of this site on December 18, 2017. Learn more.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Population Pharmacokinetic-pharmacodynamic (PK-PD) Modeling of Co-administered Gabapentin in Neuropathic Pain

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00967707
Recruitment Status : Completed
First Posted : August 28, 2009
Last Update Posted : October 12, 2011
Sponsor:
Collaborator:
Information provided by (Responsible Party):

Study Description
Brief Summary:

The primary objective of this study is to develop a pharmacokinetic (PK) and a pharmacokinetic-pharmacodynamic (PK-PD) model for gabapentin in patients with neuropathic pain.

The secondary objectives are to investigate whether adjuvant therapy of venlafaxine or donepezil contributes to 1) improved analgesic efficacy and 2) improved health-related quality of life (assessed by the SF-36 questionnaire) in neuropathic pain patients treated with gabapentin.


Condition or disease Intervention/treatment Phase
Post-traumatic Neuropathic Pain Drug: gabapentin and venlafaxine Drug: gabapentin and donepezil Phase 2

Detailed Description:

Neuropathic pain is estimated to affect 2-3 % of the population and the condition is difficult to treat with conventional analgesics. The drug of first choice is typically a tricyclic antidepressant drug (TCA) or the antiepileptic drug gabapentin. TCAs have well-documented effects, but the use is commonly interrupted due to intolerable adverse effects. Gabapentin, on the other hand, is generally well tolerated in patients. Clinical trials have proven that gabapentin is efficacious for neuropathic pain of various origins. Nevertheless, monotherapy is seldom sufficient for the management of severe neuropathic pain. Combination therapy, e.g. of gabapentin and an analgesic with complementary mechanism of action, may be a rational strategy to obtain improved results at lower doses and with fewer side effects. Although many neuropathic pain patients receive a combination of drugs, there is an absence of clinical evidence for optimal drug combinations.

Gabapentin binds to the alpha-2-delta subunit on presynaptic voltage-gated calcium channels, which results in modulation of the release of neurotransmitters from presynaptic nerve terminals. Recent studies in animal models of neuropathic pain have shown that gabapentin is effective on supraspinal structures, to activate the descending pain inhibitory noradrenergic-cholinergic cascade. Thus, it might be possible to potentiate the analgesic effect of gabapentin by concomitant administration of a drug able to prolong the action of noradrenaline or acetylcholine in the synapse cleft. In this study, the adjuvant effect of the noradrenaline and serotonin reuptake inhibitor venlafaxine and the cholinesterase inhibitor donepezil will be investigated in neuropathic pain patients treated with gabapentin.

The study consists of two periods. All patients are treated with gabapentin in the first period, and receive randomised adjuvant therapy of venlafaxine or donepezil in the second period. Repeated pain intensity ratings and blood samples for analysis of gabapentin plasma concentrations will be collected over one dosing interval of gabapentin at the end of each period.

Data will be analysed by means of nonlinear mixed effect modeling. The NONMEM programme will be used to develop models describing the PK and the PK-PD relationship of gabapentin in patients with neuropathic pain. The potential effect of concomitant treatment with venlafaxine or donepezil will be evaluated by covariate analysis in the developed PK and PK-PD models of gabapentin.


Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Population Pharmacokinetic and Pharmacodynamic Modeling of Gabapentin in Neuropathic Pain - Effect of Adjuvant Pharmacotherapy
Study Start Date : August 2009
Primary Completion Date : April 2011
Study Completion Date : September 2011

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Active Comparator: Gabapentin + venlafaxine Drug: gabapentin and venlafaxine

Week 1-6: Gabapentin monotherapy (titration to individual maximum tolerated dose or maximum 800 mg 3 times daily).

Week 7-12: Venlafaxine 75 mg once daily is added.

Active Comparator: Gabapentin + donepezil Drug: gabapentin and donepezil

Week 1-6: Gabapentin monotherapy (titration to individual maximum tolerated dose or maximum 800 mg 3 times daily).

Week 7-12: Donepezil 5 mg once daily is added.



Outcome Measures

Primary Outcome Measures :
  1. Pain intensity scorings on Numerical Rating Scale (NRS). Plasma concentrations of gabapentin. [ Time Frame: 0 - 8 hours follwing dose intake of gabapentin. during steady state ]

Secondary Outcome Measures :
  1. Health-related quality of life assessed by SF-36. Pain according to McGill Pain Questionnaire. [ Time Frame: Minimum 6 weeks following initiation of gabapentin and combination therapy, respectively ]

Eligibility Criteria

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of post-traumatic neuropathic pain
  • Spontaneous pain intensity ≥ 40 on VAS or ≥ 4 on NRS
  • Man or woman ≥ 18 years old
  • Informed consent to study participation

Exclusion Criteria:

  • Presence of other type of pain as strong as or stronger than the neuropathic pain
  • Impaired kidney function (GFR < 30 ml/min)
  • Uncontrolled cardiovascular disease/hypertonia
  • Uncontrolled narrow-angle glaucoma
  • Uncontrolled pulmonary disease
  • Epilepsia
  • Pregnancy
  • Nursing
  • Woman of childbearing potential not using contraception or planning to become pregnant during the study period
  • Disability to understand and cooperate with study procedures
  • Allergy to study medications
  • Concomitant participation in other clinical study
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00967707


Locations
Sweden
Multidisciplinary Pain Centre, Uppsala University Hospital
Uppsala, Sweden, 75185
Sponsors and Collaborators
Uppsala University
University of Copenhagen
Investigators
Principal Investigator: Stephen H. Butler, MD Uppsala University
More Information

Responsible Party: Uppsala University
ClinicalTrials.gov Identifier: NCT00967707     History of Changes
Other Study ID Numbers: GBPPKPD-09
EudraCT number 2009-010783-41
First Posted: August 28, 2009    Key Record Dates
Last Update Posted: October 12, 2011
Last Verified: September 2011

Additional relevant MeSH terms:
Neuralgia
Pain
Neurologic Manifestations
Nervous System Diseases
Peripheral Nervous System Diseases
Neuromuscular Diseases
Signs and Symptoms
Gabapentin
Venlafaxine Hydrochloride
gamma-Aminobutyric Acid
Donepezil
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anticonvulsants
Antiparkinson Agents
Anti-Dyskinesia Agents
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Anti-Anxiety Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Antimanic Agents
GABA Agents