| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.1 |
| E.1.2 | Level | HLT |
| E.1.2 | Classification code | 10044049 |
| E.1.2 | Term | Dental pain and sensation disorders |
| E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| •To evaluate the analgesic efficacy of pre-emptive doses of GW842166 (administered in two dose levels) following dental surgery |
|
| E.2.2 | Secondary objectives of the trial |
•To further evaluate the safety and tolerability of GW842166
•To evaluate the duration of analgesic effect of GW842166
•To evaluate the pharmacokinetic and pharmacodynamic relationship between drug exposure and analgesic effect of GW842166
•To compare the analgesic efficacy of GW842166 when dosed adjunctively with co-codamol to the analgesic efficacy of co-codamol alone
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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.
2. Body weight ≥ 50 kg and BMI within the range 19 - 29.9 kg/m2.
3. Women may be of non-child bearing potential or they may be of child-bearing
potential. Women of child-bearing potential must use an effective method of
contraception.
Females of non-child bearing potential are defined as:
• Post-menopausal females, being amenorrhoeic for at least 12 months, having an
appropriate clinical profile (e.g. age appropriate, vasomotor symptoms) and
having a hormonal profile (FSH and oestrogen) consistent with a diagnosis of
the menopause [where plasma FSH is elevated >40 mIU/ml and oestrogen
(oestradiol) is relatively deficient <30 pg/ml
• 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 followup
hormone level assessment.
4. Healthy as determined by a responsible physician, based on a medical evaluation
including history, physical examination, laboratory tests, cardiac monitoring and
other tests specified in this protocol. A subject with a clinical abnormality or
laboratory parameters outside the reference range for the population being studied
may be included only if the Investigator considers that the finding will not introduce
additional risk factors and will not interfere with the study procedures
5. Subject is scheduled for outpatient surgical removal of up to four third molar teeth
under local anaesthesia. At least one third molar tooth must be a fully or partially
impacted in the mandible requiring bone removal.
6. Subject agrees not to take analgesics other than protocol defined rescue analgesics
during treatment (up to 48 hrs post dose).
7. Capable of giving written informed consent, which includes compliance with the
requirements and restrictions listed in the consent form. |
|
| E.4 | Principal 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. A positive pre-study Hepatitis B surface antigen, positive Hepatitis C antibody result or positive HIV result within 3 months of screening.
3. The subject has a positive pre-study urine drug or urine/breath alcohol screen. A
minimum list of drugs that will be screened view protocol.
4. Subject has been exposed to analgesics (including prescription and over the counter NSAIDs or COX-2 inhibitors) within 48 hours or 5 half-lives (whichever is the
longer) prior to the start of surgery.
5. Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and sponsor the
medication will not interfere with the study procedures or compromise subject safety.
6. Subject is unable to refrain from alcohol, psychoactive drugs, and sedatives
including sleeping preparations (e.g. benzodiazepines) within 48 hours prior or 5
half-lives (whichever is the longer) from the start of surgery and for 48hrs post dose.
7. Following screening of 12 lead ECG and 24hr Holter ECG the subject has a significant abnormality that, in the opinion of the investigator makes them unsuitable
for the study.
8. Subject is 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 labelling, (view protocol), induced by aspirin or other NSAIDs.
9. The subject had a history of drug or alcohol abuse, or had a positive pre-study urine drug or urine/breath alcohol screen. Abuse of alcohol is defined as an average
weekly intake of greater than 21 for males and intake greater than 14 units per week for females (view protocol).
10. Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
11. Where participation in study would result in donation of blood in excess of 500 mL within a 56 day period.
12. History of sensitivity to any of the study medications, or components thereof or a
history of drug or other allergy that, in the opinion of the physician responsible, contraindicates their participation.
13. Over-The-Counter medicines are prohibited (view protocol), unless in the opinion of the Principal/Co-Investigator the medication received will not interfere with the study procedures or compromise safety.
14. The subject has received an investigational drug or participated in any other research trial within 112 days for new chemical entities and 84 days for marketed drugs or 5 half-lives, or twice the duration of the biological effect of any drug or to local requirements (whichever is longer) or prior to the first dose of current study medication.
15. The subject is known to have Gilbert's disease, or has a serum bilirubin concentration more than 1.5 times the upper limit of normal.
16. Has a supine systolic blood pressure which is outside the range of 90 to 140 mmHg, diastolic blood pressure is outside the range of 50 to 90 mmHg or heart rate is outside the range 40 to 90 bpm.
17. A marked baseline prolongation of QT/QTc interval (e.g. repeated demonstration of QTc interval ≥450ms)
• A history of additional risk factors for Torsade de Pointes (TdP) e.g. heart
failure, hypokalaemia, family history of Long QT syndrome.
• The use of concomitant medications that prolong the QT/QTc interval
18. Has a history or presence of gastro-intestinal, hepatic or renal disease or other
condition known to interfere with the absorption, distribution, metabolism or
excretion of drugs.
Male subjects only:
1. An unwillingness of male subjects to abstain from sexual intercourse with pregnant or lactating women view protocol.
2. An unwillingness of the male subject to use a condom/spermicide in addition to
having their female partner use another form of contraception view protocol.
Female subjects of child bearing potential:
1. 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 view protocol.
2. The first day of the last menstrual period was more than 10 days prior to the day of dosing with study medication.
3. An unwillingness of the female subject to use an appropriate form of contraception. View protocol for appropriate forms of contraception.
4. Male partner sterilisation (vasectomy) prior to the female subject's entry into the
study and is the sole partner for that female subject.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| • Weighted mean of the pain intensity over the 10 hours post-dose as measured by the VAS (Visual Analogue Scale) |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | Yes |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
|
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 6 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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