A double blind, double dummy, randomized, placebo-controlled, 4 period cross-over study to examine the effect of PF-063782865 on evoked pain endpoints in healthy volunteers using pregabalin as a positive control
- Conditions
- Chronic pain10029305
- Registration Number
- NL-OMON40624
- Lead Sponsor
- Pfizer
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 20
1. Healthy male subjects between the ages of 18 and 55 years, inclusive. Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12-lead ECG or clinical laboratory tests.
2. Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs).
3. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
4. Subjects who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures.
1. Evidence or history of clinically significant hematological, renal, endocrine,
pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or
allergic disease (including drug allergies, but excluding untreated, asymptomatic,
seasonal allergies at the time of dosing).
2. Any condition possibly affecting drug absorption (eg, gastrectomy).
3. A positive urine drug screen.
4. History of regular alcohol consumption exceeding 21 drinks/week for males
(1 drink = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces
(45 mL) of hard liquor) within 6 months of Screening.
5. Treatment with an investigational drug within 30 days (or as determined by the local
requirement) or 5 half-lives preceding the first dose of study treatment (whichever is
longer).
6. Screening supine blood pressure >140 mm Hg (systolic) or >90 mm Hg (diastolic),
following at least 5 minutes of supine rest. If blood pressure (BP) is >140 mm Hg
(systolic) or >90 mm Hg (diastolic), the BP should be repeated two more times and
the average of the three BP values should be used to determine the subject*s
eligibility.
7. 12-lead ECG demonstrating QTc >450 msec or a QRS interval >120 msec at
Screening. If QTc exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be
repeated two more times and the average of the three QTc or QRS values should be
used to determine the subject*s eligibility.
8. Any current, clinically significant, known medical condition in particular any existing
conditions that would affect sensitivity to cold (such as atherosclerosis, Raynaud*s
disease, urticaria, hypothyroidism) or pain (parasthesia etc).
9. Subjects indicating nociceptive tests intolerable at screening or achieving tolerance at
>80% of maximum input intensity for any nociceptive test for cold, heat, pressure and
electrical tests.
10. Consume on average >8 units per day of (methyl)xanthine (eg coffee, tea, cola,
chocolate) and not able to refrain from use during each stay at the CRU clinic.
11. Subjects with ANY of the following abnormalities in clinical laboratory tests at
screening, as assessed by the study-specific laboratory and confirmed by a single
repeat, if deemed necessary:
- Aspartate transaminase (AST)/serum glutamic oxaloacetic transaminase (SGOT)
or alanine transaminase (ALT)/serum glutamic pyruvic transaminase (SGPT) * 1
x upper limit of normal (ULN);
- Total bilirubin >1.5 x ULN; subjects with a history of Gilbert's syndrome may
have a direct (conjugated) bilirubin measured and would be eligible for this study
provided the direct bilirubin is > ULN.
12. Male subjects with partners currently pregnant; male subjects of childbearing
potential who are unwilling or unable to use a highly effective method of
contraception as outlined in this protocol for the duration of the study and for 3
months after the last dose of study treatment.
13. Use of prescription or nonprescription drugs and dietary supplements within 7 days or
5 half-lives (whichever is longer) prior to the first dose of study treatment. Herbal
supplements must be discontinued at least 28 days prior to the first dose of study
treatment.
14. Blood donation (excluding plasma donations) of approximately 500 mL or more
within 3 months of screening.
15. Known hypersensitivity to the investigational
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Thermal Pain (Normal Skin): Pain Detection Threshold (PDT).<br /><br>Thermal Pain (Ultraviolet B (UVB) Skin): Pain Detection Threshold (PDT).<br /><br>Electrical Stair (pre-cold pressor): Pain Tolerance Threshold (PTT).<br /><br>Pressure Pain: Pain Tolerance Threshold (PTT).<br /><br>Cold Pressor: Pain Tolerance Threshold (PTT).</p><br>
- Secondary Outcome Measures
Name Time Method <p>Electrical Stair (pre-cold pressor): Pain Detection Threshold (PDT), Area Under<br /><br>the Visual Analogue Scale (VAS) pain Curve (AUC), and post-test VAS.<br /><br>Electrical Stair (post-cold pressor): PDT, PTT, AUC, and post-test VAS.<br /><br>Conditioned Pain Modulation Response (change from electrical stair pre- and<br /><br>post cold pressor): PDT, PTT, AUC, and post-test VAS.<br /><br>Pressure Pain: PDT, AUC, and post-test VAS.<br /><br>Cold Pressor: PDT, AUC, and post-test VAS.<br /><br>PF-06372865 plasma pharmacokinetic parameters: Cmax, AUClast, , AUCinf, Tmax<br /><br>and t* (if data permits).<br /><br>Pregabalin concentrations at the time of pharmacodynamic testing from 0.5-10<br /><br>hours.<br /><br>Adverse events, laboratory safety, blood pressure, pulse rate and<br /><br>electrocardiogram m(ECG).</p><br>