| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| 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 describe the single dose response relationship of the dose range of 7.5 to 60mg of GW856553 on circulating serum CRP levels |
|
| E.2.2 | Secondary objectives of the trial |
• To describe the single dose response relationship of GW856553 on circulating serum IL-6 levels.
• To describe the effect of GW856553 on circulating biomarker levels.
• To collect plasma drug concentration data to allow characterisation of the pharmacokinetics (PK) of GW856553 and GSK198602, a known metabolite of GW856553, following a single oral dose of GW856553 in rheumatoid arthritis patients.
• To explore the relationship between plasma GW856553 concentration and CRP change.
|
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
A subject will be eligible for inclusion in this study only if all of the following criteria apply:
1. The patient is ≥ 18 years of age.
2. To be eligible, female patients must have a negative pregnancy test (i.e. serum beta hCG test) and be of:
a) non-childbearing potential (i.e. physiologically incapable of becoming
pregnant). This includes any female who is post-menopausal. For the purposes
of this study, post menopausal is defined as being amenorrhoeic for greater than
2 years with an appropriate clinical profile, e.g. age appropriate, history of
vasomotor symptoms. Postmenopausal status will be confirmed by serum FSH
and oestradiol concentrations at screening. Surgical sterility will be defined as
females who have had a hysterectomy and/or bilateral oophorectomy or tubal
ligation.
OR
b) childbearing potential and agrees to commit to one of the protocol-approved
methods of contraception, when used consistently and in accordance with both
the product label and the instructions of a physician, as indicated in Section 7.1.
3. The patient has a body mass index (BMI) within the range of 18.5-35.0 Kg/m2.
4. The patient has a diagnosis of RA according to the revised 1987 criteria of the American College of Rheumatology (ACR).
5. The patient has serum CRP ≥ 10mg/l at screening (maximum 1 week prior to dosing with investigational product).
6. The patient has ≥ 3/66 swollen or ≥ 3/68 tender/painful joints at screening.
7. The patient has urea and creatinine within normal range at screening.
8. The patient must have liver function tests (ALT, AST and gamma GT) within 1.5 times the upper limit of normal (ULN); ALP within 2 times the upper limit of normal and total bilirubin within normal range at screening.
9. The patient must be on stable weekly methotrexate (2.5mg – 25mg) for at least eight weeks prior to screening (i.e. dose unchanged throughout the 8 week period).
10. Any additional oral anti-rheumatic therapies (which may include sulphasalazine [≤ 3g/day] or hydroxychloroquine or glucocorticoid ≤ 10mg/day) must be stable for at least eight weeks prior to screening.
11. Any additional oral symptomatic relief therapy (which may include NSAIDs or COX-2 inhibitors) must be stable for at least 2 weeks prior to screening.
12. The patient must be capable of giving informed consent and can comply with the study requirements and timetable.
13. Subjects must have a QTc(b) of less than 430msecs for males and 450msecs for females at screening.
|
|
| E.4 | Principal exclusion criteria |
A subject will not be eligible for inclusion in this study if any of the following criteria apply:
1. The patient has a three month prior history of alcohol use > 21 units per week for males and > 14 units per week for females (1 unit of alcohol = ½ pint [284mL] of beer, 125mL of wine or 25mL of spirits).
2. The patient has any history of liver disease within 6 months of screening.
3. The patient is infected with Hepatitis B or Hepatitis C.
4. The patient has an active infection.
5. The patient has a history of elevated liver function tests on more than one occasion (ALT, AST or total bilirubin > 1.5 x ULN) in the past 3 months.
6. The patient is receiving a biological anti-rheumatic therapy.
7. The patient has a significant cardiac, pulmonary, metabolic, renal, hepatic or gastrointestinal condition that, in the opinion of the investigator and/or GlaxoSmithKline (GSK) medical monitor, places the patient at an unacceptable risk as a participant in this trial.
8. The patient has participated in a clinical trial within the 3 months prior to the study onset for non-biological therapy; or within 4 months of a biological therapy.
9. The patient has haemoglobin (Hb) < 9 or platelet count < 150000/mm3
10. The patient has a resting systolic blood pressure persistently > 150mmHg or diastolic blood pressure persistently > 90mmHg at screening.
11. An unwillingness of male subjects to abstain from sexual intercourse with pregnant or lactating women; or 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: an intrauterine device (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 completion of follow-up procedures.
12. Patients who are pregnant or nursing.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| • CRP levels 72 hours post-dose. |
|
| 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 | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| 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 | No |
| E.8.1.4 | Double blind | Yes |
| 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) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| 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.8.5 | The trial involves multiple Member States | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| 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
|
| End of trial is the last visit of the last subject. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 4 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 4 |
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