HyperalgesiaPhase 1NCT00387413
A Study Of GSK189254 And Duloxetine In The Electrical Hyperalgesia Model Of Healthy Volunteers
A Phase 1 study testing Duloxetine and GSK189254 in people with Hyperalgesia, run by GlaxoSmithKline at 1 site in United Kingdom.
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). Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Hyperalgesia
- What is being tested?
- Duloxetine and GSK189254
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 2 Oct 2006to 31 May 2007
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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).
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- 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.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
GSK Investigational Site
Cambridge, Cambridgeshire, CB2 0QQ
About this study
Official title: A Double-blind, Double-dummy, Placebo-controlled, Incomplete Block, Two Period Crossover Study of the Histamine H3 Antagonist GSK189254 and Duloxetine in the Electrical Hyperalgesia Model of Central Sensitisation in Healthy Volunteers
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.
- Conditions
- Hyperalgesia
- Being tested
- Duloxetine, GSK189254, GSK189254 Placebo, Duloxetine Placebo
- Keywords
- Duloxetine, GSK189254, Healthy volunteers, Phase I., Electrical hyperalgesia model
- Medical subject headings
- Hyperalgesia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DuloxetineDrug
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.
GSK189254Drug
Also called Duloxetine
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 PlaceboDrug
Subjects will receive Placebo matching GSK189254 for 3 weeks in each period.
Duloxetine PlaceboDrug
Subjects will receive Placebo matching Duloxetine for 3 weeks in each period.
| Study group | Role | What they receive |
|---|---|---|
| Treatment Arm A1 | Experimental | In treatment Arm A1 Period 1 subject will receive 50 mcg GSK189254 plus Duloxetine Placebo in Week 1, in Week 2 subject will receive 100 mcg GSK189254 plus Duloxetine Placebo and in Week 3 subject will receive GSK189254 Placebo plus Duloxetine Placebo. In treatment Arm A1 Period 2 subject will receive GSK189254 Placebo plus Duloxetine Placebo for all 3 Weeks. There will be a washout of approximately one week between periods 1 and 2. Receives: Drug: GSK189254; Drug: GSK189254 Placebo; Drug: Duloxetine Placebo |
| Treatment Arm A2 | Experimental | In treatment Arm A2 Period 1 subject will receive GSK189254 Placebo plus Duloxetine Placebo for all 3 Weeks. In treatment Arm A2 Period 2 subject will receive 50 mcg GSK189254 plus Duloxetine Placebo in Week 1, in Week 2 subject will receive 100 mcg GSK189254 plus Duloxetine Placebo and in Week 3 subject will receive GSK189254 Placebo plus Duloxetine Placebo. There will be a washout of approximately one week between periods 1 and 2. Receives: Drug: GSK189254; Drug: GSK189254 Placebo; Drug: Duloxetine Placebo |
| Treatment Arm B1 | Experimental | In treatment Arm B1 Period 1 subject will receive 30 milligram (mg) Duloxetine plus GSK189254 Placebo in Week 1, in Week 2 60 mg Duloxetine plus GSK189254 Placebo and in Week 3 30 mg Duloxetine plus GSK189254 Placebo. In treatment Arm B1 Period 2 subject will receive GSK189254 Placebo plus Duloxetine Placebo for all 3 Weeks. There will be a washout of approximately one week between periods 1 and 2. Receives: Drug: Duloxetine; Drug: GSK189254 Placebo; Drug: Duloxetine Placebo |
| Treatment Arm B2 | Experimental | In treatment Arm B2 Period 1 subject will receive GSK189254 Placebo plus Duloxetine Placebo for all 3 Weeks. In treatment Arm B2 Period 2 subject will receive 30 milligram (mg) Duloxetine plus GSK189254 Placebo in Week 1, in Week 2 60 mg Duloxetine plus GSK189254 Placebo and in Week 3 30 mg Duloxetine plus GSK189254 Placebo. There will be a washout of approximately one week between periods 1 and 2. Receives: Drug: Duloxetine; Drug: GSK189254 Placebo; Drug: Duloxetine Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area of pin-prick hyperalgesia Area of touch-evoked allodynia
Measured: The mortality of above measurements at 7 months, functional status for each subject at 8-10 weeks.
Secondary outcomes (1)
Ongoing pain intensity rating Area and intensity of flare Mood and alertness
Measured: The mortality for above measurements at 7 months, functional status for each subject 8-10 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2006 (estimated)
- Study start2 Oct 2006
- Primary completion31 May 2007
- Study completion31 May 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HyperalgesiaStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00387413
- Sponsor's protocol ID
- H3A106308
- Status last verified
- Aug 2017
- First submitted
- 11 Oct 2006
- Last updated
- 7 Aug 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-blind, Double-dummy, Placebo-controlled, Incomplete Block, Two Period Crossover Study of the Histamine H3 Antagonist GSK189254 and Duloxetine in the Electrical Hyperalgesia Model of Central Sensitisation in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT00387413
- Acronym / sponsor ID
- H3A106308
- Conditions
- Hyperalgesia
- Keywords
- Duloxetine, GSK189254, Healthy volunteers, Phase I., Electrical hyperalgesia model
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 2 Oct 2006 (actual)
- Primary completion
- 31 May 2007 (actual)
- Study completion
- 31 May 2007 (actual)
- First posted
- 13 Oct 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Treatment Arm A1 | Experimental | Drug: GSK189254, Drug: GSK189254 Placebo, Drug: Duloxetine PlaceboIn treatment Arm A1 Period 1 subject will receive 50 mcg GSK189254 plus Duloxetine Placebo in Week 1, in Week 2 subject will receive 100 mcg GSK189254 plus Duloxetine Placebo and in Week 3 subject will receive GSK189254 Placebo plus Duloxetine Placebo. In treatment Arm A1 Period 2 subject will receive GSK189254 Placebo plus Duloxetine Placebo for all 3 Weeks. There will be a washout of approximately one week between periods 1 and 2. |
| Treatment Arm A2 | Experimental | Drug: GSK189254, Drug: GSK189254 Placebo, Drug: Duloxetine PlaceboIn treatment Arm A2 Period 1 subject will receive GSK189254 Placebo plus Duloxetine Placebo for all 3 Weeks. In treatment Arm A2 Period 2 subject will receive 50 mcg GSK189254 plus Duloxetine Placebo in Week 1, in Week 2 subject will receive 100 mcg GSK189254 plus Duloxetine Placebo and in Week 3 subject will receive GSK189254 Placebo plus Duloxetine Placebo. There will be a washout of approximately one week between periods 1 and 2. |
| Treatment Arm B1 | Experimental | Drug: Duloxetine, Drug: GSK189254 Placebo, Drug: Duloxetine PlaceboIn treatment Arm B1 Period 1 subject will receive 30 milligram (mg) Duloxetine plus GSK189254 Placebo in Week 1, in Week 2 60 mg Duloxetine plus GSK189254 Placebo and in Week 3 30 mg Duloxetine plus GSK189254 Placebo. In treatment Arm B1 Period 2 subject will receive GSK189254 Placebo plus Duloxetine Placebo for all 3 Weeks. There will be a washout of approximately one week between periods 1 and 2. |
| Treatment Arm B2 | Experimental | Drug: Duloxetine, Drug: GSK189254 Placebo, Drug: Duloxetine PlaceboIn treatment Arm B2 Period 1 subject will receive GSK189254 Placebo plus Duloxetine Placebo for all 3 Weeks. In treatment Arm B2 Period 2 subject will receive 30 milligram (mg) Duloxetine plus GSK189254 Placebo in Week 1, in Week 2 60 mg Duloxetine plus GSK189254 Placebo and in Week 3 30 mg Duloxetine plus GSK189254 Placebo. There will be a washout of approximately one week between periods 1 and 2. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (13 listed)
- 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.
Key exclusion criteria (21 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DuloxetineSubjects 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. | Drug | Treatment Arm B1, Treatment Arm B2 |
| GSK189254Also: DuloxetineSubjects 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. | Drug | Treatment Arm A1, Treatment Arm A2 |
| GSK189254 PlaceboSubjects will receive Placebo matching GSK189254 for 3 weeks in each period. | Drug | Treatment Arm A1, Treatment Arm A2, Treatment Arm B1, Treatment Arm B2 |
| Duloxetine PlaceboSubjects will receive Placebo matching Duloxetine for 3 weeks in each period. | Drug | Treatment Arm A1, Treatment Arm A2, Treatment Arm B1, Treatment Arm B2 |
Primary outcome
Area of pin-prick hyperalgesia Area of touch-evoked allodynia
Time frame: The mortality of above measurements at 7 months, functional status for each subject at 8-10 weeks.
1 secondary outcome
Ongoing pain intensity rating Area and intensity of flare Mood and alertness
Time frame: The mortality for above measurements at 7 months, functional status for each subject 8-10 weeks.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2017.
- Results for study H3A106308 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Duloxetine and GSK189254 in people with Hyperalgesia, run by GlaxoSmithKline at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area of pin-prick hyperalgesia Area of touch-evoked allodynia (time frame: The mortality of above measurements at 7 months, functional status for each subject at 8-10 weeks.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2017.