A multi-centre, randomised, single blind, placebo controlled, parallel group study to examine the effect of single doses of SB-705498, a TRPV1 receptor antagonist, on pain following third molar tooth extractio

• Conditions: Dental pain

• Registration Number: EUCTR2005-004481-16-GB
• Lead Sponsor: GlaxoSmithKline Research and Development

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2005-10-21
• Last Update Posted: 18 April 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 140

Inclusion Criteria

A subject will be eligible for inclusion in this study only if all of the following criteria apply:
1. Female or male subjects aged 18 to 50. Women may be of child bearing potential or of non-child bearing potential. Women of child bearing potential must use an effective method of contraception (see below).
Females of non-child bearing potential are defined as:
• Post-menopausal females, being amenorrhoeic for at least 2 years with an appropriate clinical profile, e.g., age appropriate, history of vasomotor symptoms. However, if indicated this should be confirmed by oestradiol and FSH levels consistent with menopause (according to local laboratory ranges).
• Pre-menopausal females with a documented hysterectomy (medical report verification) and/or bilateral oophorectomy. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment.
2. Subject is healthy. Healthy subjects are defined as individuals who are not taking any regular medication and are free from clinically significant illness or disease as determined by their medical history (including family history), physical examination, 12-lead ECG, Holter monitor, laboratory studies, and other tests specified in this protocol.
3. Subject is scheduled for outpatient surgical removal of up to four third molar teeth under local anesthesia. At least one third molar tooth must be a fully or partially impacted in the mandible requiring bone removal;
4. Subject agrees not to take analgesics other than protocol defined rescue analgesics during treatment (up to 24 hrs post dose)
5. Subject has the ability to read, comprehend, and record information required by protocol;
6. Subject is willing and able to provide signed and dated written informed consent prior to study participation.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

A subject will not be eligible for inclusion in this study if any of the following criteria apply:
1. Subject has a history or presence of significant organ disease or mental illness;
2. Subject has been exposed to analgesics other than aspirin (including prescription and over the counter NSAIDs or COX-2 inhibitors) within 24 hours prior to the start of surgery;
3. Subject is unable to refrain from alcohol, psychoactive drugs, and sedatives including sleeping preparations (e.g . benzodiazepines) within 24 hours prior to the start of surgery and for the duration of their participation in the study
4. Following screening (and 24 h Holter ECG) the subject has a significant abnormality that, in the opinion of the investigator makes them unsuitable for the study.
5. Subject with a known allergy to or judged by the investigator not to be a suitable candidate for ibuprofen or co-codamol therapy based on medical history, concomitant medications, and concurrent systemic disease as described in the product labeling, e.g., peptic ulcer disease, angioedema, bronchospastic reactivity (e.g., asthma), rhinitis and nasal polyps induced by aspirin or other NSAIDs;
6. The subject had a history of drug or alcohol abuse, or had a positive pre-study urine drug / alcohol breath screen. Abuse of alcohol is defined as an average weekly intake of greater than 21 units or an average daily intake of greater than three units for males and intake greater than 14 units per week or an average daily intake of greater than two units for females. One unit is equivalent to a half-pint (220 mL) of beer or one (25 mL) measure of spirits or one glass (125 mL) of wine.
7. Subject has participated, or is participating in, a clinical study in which they have been exposed to an investigational drug or device during the past 30 days;
8. Subject has donated blood (450 mL or more) within the previous month.
Male subjects only:
9. An unwillingness of male subjects to abstain from sexual intercourse with pregnant or lactating women from the time of the first dose of study medication until five half-lives following administration of the last dose of study medication.
10. An unwillingness of the male subject to use a condom/spermicide in addition to having their female partner use another form of contraception such as IUD, diaphragm with spermicide, oral contraceptives, injectable progesterone, subdermal implants or a tubal ligation if the woman could become pregnant from the time of the first dose of study medication until 84 days following administration of the last dose of study medication.
Female subjects of child bearing potential:
11. Female subjects who are pregnant, breast feeding, or have a positive serum pregnancy test or a positive urine pregnancy test either at screening or pre-dose on each dosing session.
12. An unwillingness of the female subject to use an appropriate form of contraception. Appropriate forms of contraception are defined as:
a. Abstinence – The lifestyle of the female should be such that there is complete abstinence from intercourse from at least the commencement of their last normal period prior to the first dose of study medication and to continue until the first normal period (defined as normal for the woman, both in terms of duration and quantity of menses) after treatment or 15 days after the last dose of medication, whichever is the longest.
b. One of the following methods is acceptable as the sole method of contraception if there is indisputabl

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the analgesic efficacy of SB-705498 following dental surgery.;Secondary Objective: To further evaluate the safety and tolerability of SB-705498<br>To evaluate the duration of analgesic effect for SB-705498<br>To evaluate the pharmacokinetic and pharmacodynamic relationship between drug exposure and analgesic effect of SB-705498<br>To compare the analgesic efficacy of SB-705498 when dosed adjunctively with ibuprofen to the analgesic efficacy of ibuprofen alone. <br>;Primary end point(s): Weighted mean of the change from baseline in pain intensity (i.e. pain intensity difference) over the 10 hours post-dose.