Clinical trial NCT00281684: SB-705498 Dental Pain Study After Tooth Extraction
Official title: 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 Extraction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Toothache
Keywords: Acute Pain
Dental Pain
Vanilloid
VR1
TRPV1
Inflammation
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2006-01-25
Enrollment: 145
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This clinical trial is a multi centre, randomised, single-blind, parallel group, placebo-controlled, single oral dose study with a positive control arm. Patients previously scheduled for 3rd molar tooth extraction, who are otherwise healthy, will be recruited. Upon completion of surgery, e.g. prior to established pain, patients will be randomised to treatment (SB-706598, placebo or co-codamol) and dosed with the study medication


Eligibility criteria: Inclusion criteria:

* 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.
* 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.
* 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;
* Subject agrees not to take analgesics other than protocol defined rescue analgesics during treatment (up to 24 hrs post dose)
* Subject has the ability to read, comprehend, and record information required by protocol;
* Subject is willing and able to provide signed and dated written informed consent prior to study participation.

Exclusion criteria:

* Subject has a history or presence of significant organ disease or mental illness;
* 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;
* 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
* 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.
* 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;
* 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.
* 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;
* Subject has donated blood (450 mL or more) within the previous month.
* Male subjects only:
* 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.
* 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:
* 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.
* An unwillingness of the female subject to use an appropriate form of contraception. Appropriate forms of contraception are defined as:
* 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.
* One of the following methods is acceptable as the sole method of contraception if there is indisputable data that it is \>99% effective otherwise it should be used with a barrier method (condom or occlusive cap {diaphragm or cervical/vault caps} used with spermicidal foam/gel/film/cream/suppository):
* Established use of oral, injected or implanted hormonal methods of contraception from at least the commencement of their last normal period prior to the first dose of study medication. Subjects using hormonal contraception should use a barrier method in addition from the first dose of study medication until their next normal period following the end of the study.
* Documented tubal ligation.
* Documented placement of an intrauterine device (IUD) or intrauterine system (IUS).
* Male partner sterilisation (vasectomy) prior to the female subject's entry into the study and is the sole partner for that female subject.

Primary outcomes:
measure: Mean of Pain Intensity Based on the Visual Analogue Scale (VAS)
timeFrame: Up to 10 hours post-dose
Secondary outcomes:
measure: Change From Baseline in the Pain Intensity Based on the Verbal Rating Scale (VRS) up to 10 Hours Post Baseline
timeFrame: Up to 10 hours post Baseline (Day 1)
measure: Change From Baseline in the Pain Intensity Based on the VAS up to 10 Hours Post-Baseline
timeFrame: Baseline (Day 1) to 10 hours post Baseline
measure: Elapsed Time From Study Drug Administration to Rescue Analgesic Request
timeFrame: Within 24 hours of administration of study drug
measure: Number of Participants With Different Global Evaluation or Overall Impression of Study Medication Use and at 10 and 24 Hours Post Randomization
timeFrame: Prior to first rescue medication use and at 10 and 24 hours post randomization
measure: VAS Mean Pain Scores From the Time of Rescue Medication up to 10 Hours Post Randomization
timeFrame: From the time of rescue medication to 10 hours post randomization
measure: Number of Participants Requiring Rescue Medication Over Time
timeFrame: Up to 10 hour post-dose
measure: Number of Participants From First Rescue Medication Use to Second Rescue Analgesic Request
timeFrame: From first dose of rescue medication to second dose of rescue medication
measure: Number of Participants With Adverse Events (AE) Over Time
timeFrame: Up to Follow-up (28 days)
measure: Number of Participants With Abnormal Electrocardiogram (ECG) Findings
timeFrame: 28 days
measure: Number of Participants With Second Degree Atrioventricular Block Over 24 Hours by Holter Tape
timeFrame: Up to 24 hours post-dose
measure: Change From Baseline for Vital Signs- Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
timeFrame: Baseline (Day 1) to 24 hours post Baseline
measure: Change From Baseline for Vital Signs-Body Temperature
timeFrame: Baseline (Day 1) to 24 hours post Baseline
measure: Number of Participants With Clinical Chemistry/ Hematology Values/ Serum Hormones Values of Potential Clinical Concern
timeFrame: Up to 28 days
measure: Number of Participants With Abnormal Urine Parameters
timeFrame: Up to 28 days
measure: Area Under Curve (AUC)(0-rescue) and AUC(0-t) of SB705498
timeFrame: At pre-dose on Baseline (Day 1) and at between 20-40 minutes and at 1, 1.5, 2, 3, 4, 6, 8, 10 hours post dose and at final follow-up (Day 28)
measure: Plasma Concentrations: Average Concentration (C-avg) [0-rescue] and Maximum Concentration (C-max) of SB705498
timeFrame: At pre-dose on Baseline (Day 1) and at between 20-40 minutes and at 1, 1.5, 2, 3, 4, 6, 8, 10 hours post dose and at final follow-up (Day 28)
measure: Time Prior to the First Measurable Concentration (T-lag) and Time to Maximum Observed Plasma Concentration (T-max)
timeFrame: At pre-dose (Baseline) and at between 20-40minutes and at 1, 1.5, 2, 3, 4, 6, 8, 10 hours post randomization and at final follow-up (Day 28)
Other outcomes:
Locations:
city: Verona
country: Italy
facility: GSK Investigational Site
state: Veneto
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Croydon
country: United Kingdom
facility: GSK Investigational Site
state: Surrey
city: Leeds
country: United Kingdom
facility: GSK Investigational Site
city: Manchester
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: