SB-705498 Dental Pain Study After Tooth Extraction
Condition: Toothache
MeSH terms: Toothache
Intervention: SB705498 400 mg; SB705498 1000 mg; Placebo; Co-Codamol
Intervention description: SB705498 400 mg; SB705498 1000 mg; Placebo; Co-Codamol
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Enrollment: 145.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: No
Keywords: Acute Pain; Dental Pain; Vanilloid; VR1; TRPV1; Inflammation

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.