Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00387413
Other study ID # H3A106308
Secondary ID
Status Completed
Phase Phase 1
First received October 11, 2006
Last updated August 3, 2017
Start date October 2, 2006
Est. completion date May 31, 2007

Study information

Verified date August 2017
Source GlaxoSmithKline
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

GSK189254 is a highly potent histamine 3 (H3) receptor antagonist which has demonstrated efficacy in the reduction of mechanical hyperalgesia and allodynia in the chronic constriction injury pre-clinical model of neuropathic pain (NP). The mechanism of action of GSK 189254 in the pain model is hypothesised to be via enhanced release of monoamines in the central nervous system (CNS). A similar mechanism of action has also been shown for duloxetine. In this phase I study, the safety and efficacy of GSK189254 will be investigated in the electrical hyperalgesia (EH) model in healthy volunteers to build confidence that the preclinical efficacy demonstrated by this compound will translate into patients.

This study will be conducted as a double-blind, double-dummy, placebo-controlled, incomplete block, two period crossover study. Up to 40 healthy male or female volunteers, aged 18-45 years old, will be randomised into the study in order to achieve 32 evaluable subjects. Subjects will undergo two 3-week treatment periods and will be randomised to receive placebo and either GSK189254 (up to 100µg once daily) or duloxetine (up to 60mg daily). There will be a one week washout between treatment periods. The effects of repeated oral dosing of GSK189254 and duloxetine on secondary hyperalgesia in the EH model will be determined. Subject: GSK189254, Neuropathic pain (NP), H3 antagonist, duloxetine, Electrical hyperalgesia, Phase I, Healthy volunteers, Double blind, Safety, tolerability.


Recruitment information / eligibility

Status Completed
Enrollment 40
Est. completion date May 31, 2007
Est. primary completion date May 31, 2007
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 18 Years to 45 Years
Eligibility Inclusion Criteria:

- He/she is a healthy subject.

- Women of child bearing potential must have a negative pregnancy test at screening and have undergone, or confirm regular use of one of the following:

Female sterilisation Sterilisation of male partner Practising a clinically accepted method of contraception during the study and for at least one month prior to baseline and one month following completion of the study.

- Has Caucasian skin colour.

- Body weight > 50kg and BMI within the range 18.5 to 29.9kg/m2 inclusive.

- Non smoker.

- Satisfactory pre-study medical within 28 days prior to the start of the study.

- No abnormality on clinical examination

- No abnormality on clinical chemistry or haematology.

- Negative pre-study urine drug screen and cotinine test.

- Signed and dated written informed consent prior to admission to the study.

- The subject is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions.

- Available to complete the study.

Exclusion Criteria:

- The subject has a positive pre-study urine drug/alcohol screen. A minimum list of drugs that will be screened for include Amphetamines, Barbiturates, Cocaine, Opiates, Cannabinoids, Methadone and Benzodiazepines.

- The subject has a history of drug or other allergy, that, in the opinion of the responsible physician, contraindicates their participation.

- A positive pre-study Hepatitis B surface antigen, positive Hepatitis C antibody or positive HIV results.

- History of clinically significant psychiatric disease, or presence of depressive disorder as defined by HAD depression score >8, or presence of anxiety disorder as defined by HAD anxiety score >8.

History or presence of insomnia or other sleep disorders.

- A QTcB interval < 430msec (men) or < 450msec (women).

- The subject has donated >500 mls of blood within 56 days prior to the first dose.

- Abuse of alcohol defined as an average daily intake of greater than 3 units for men and 2 units for the women.

- The subject has a history or presence of drug/substance abuse as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria.

- The subject has participated in a study with a new molecular entity during the previous 112 days or any other trial during the previous 84 days.

- The subject is currently taking regular (or a course of) medication whether prescribed or not. Such a subject may be included if the Investigator considers that this does not compromise safety or study procedures.

- Has received prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days or 5 half-lives whichever is the longer, prior to the first dose of study medication

- The subject has a history of chronic pain before screening.

- The subject has ingested or used a topical preparation containing aspirin or other non-steroidal anti-inflammatory drugs or paracetamol or other analgesic medication in the 7 days prior to the screening visit.

- The subject has used any topical steroid in the previous 30 days.

- The subject has used any topical capsaicin preparations on the forearms in the previous 30 days.

- The subject suffers from eczema, psoriasis or any other acute or chronic dermatological problem.

- The subject does not produce an area of allodynia or hyperalgesia to the EH model at screening

- The subject is unable to tolerate the EH model, including anxiety or atypical response to the model.

- The subject has any abnormality on diagnostic EEG at screening, or a history or presence of seizures or risk factors for seizure.

- The subject has any other medical condition that in the opinion of the Investigator would compromise the safety of the subject or the subject's ability to complete the study.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Duloxetine
Subjects will be receive hard gelatin capsules of Duloxetine at 30mg once daily for one week and 60mg once daily for the second week in Treatment Arm B.
GSK189254
Subjects will receive film coated tablet of GSK189254 at 50 mcg once daily for a one week and 100 mcg once daily for the second week in Treatment Arm A.
GSK189254 Placebo
Subjects will receive Placebo matching GSK189254 for 3 weeks in each period.
Duloxetine Placebo
Subjects will receive Placebo matching Duloxetine for 3 weeks in each period.

Locations

Country Name City State
United Kingdom GSK Investigational Site Cambridge Cambridgeshire

Sponsors (1)

Lead Sponsor Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Area of pin-prick hyperalgesia Area of touch-evoked allodynia The mortality of above measurements at 7 months, functional status for each subject at 8-10 weeks.
Secondary Ongoing pain intensity rating Area and intensity of flare Mood and alertness The mortality for above measurements at 7 months, functional status for each subject 8-10 weeks.
See also
  Status Clinical Trial Phase
Completed NCT01301079 - Evaluation of the Effect of Ketamine on Remifentanil-induced Hyperalgesia Phase 3
Completed NCT00833755 - Effect of Ketamine on Opioid-Induced Hyperalgesia N/A
Completed NCT00279032 - GW406381 In Patients With Peripheral Nerve Injury Phase 1
Completed NCT03793790 - The Role of Learning in Nocebo Hyperalgesia N/A
Completed NCT03985995 - Pain Response to Cannabidiol in Induced Acute Nociceptive Pain, Allodynia and Hyperalgesia By Using a Model Mimicking Acute Pain in Healthy Adults N/A
Completed NCT04199858 - Electrophysiological Correlates of Nocebo Effects on Pain N/A
Completed NCT02938455 - DNA Methylation and Perioperative Pain Treatment
Not yet recruiting NCT02934763 - Opioid Induced Hyperalgesia (OIH) Modulation With Propranolol Phase 4
Completed NCT02253966 - Preoperative Intraarticular Injection of Methylprednisolone in Patients Scheduled for Total Knee-arthroplasty Phase 2
Completed NCT02653703 - L-menthol as a Topical Counter-irritant to TRPA1-induced Neurogenic Inflammation and Pain N/A
Terminated NCT01615510 - Evaluation of the Antihyperalgesic Effect of Tapentadol in Two Human Experimental Models Phase 1
Completed NCT01702389 - Opioid-induced Hyperalgesia After Remifentanil Infusion Phase 4
Completed NCT00218374 - Dextromethorphan, Gabapentin, and Oxycodone to Treat Opioid-Induced Hyperalgesia N/A
Completed NCT04197154 - Pain-related Fear as a Facilitator of Nocebo Hyperalgesia N/A
Completed NCT02976337 - Effect of High-dose Naloxone Following Third Molar Extraction Phase 2
Completed NCT03354624 - Cortical Neuroplasticity by Muscle Pain of Pain-induced Plasticity N/A
Completed NCT02596360 - Dextromethorphan Effect on Central Sensitization to Pain in Healthy Volunteers Phase 1
Recruiting NCT01480765 - Preventing Pain After Heart Surgery Phase 4
Recruiting NCT01015482 - The Effect of High-dose Remifentanil on Established Sunburn-induced Hyperalgesia in Human Volunteers (HighDose RemiSun) Phase 4
Completed NCT01025245 - Effect of Intraoperative Magnesium on Remifentanil-induced Postoperative Hyperalgesia After Thyroidectomy Phase 4