To investigate the ability of PF-05089771 to demonstrate analgesic properties in healthy subjects for pre-specified primary endpoints using a panel of pain tests.
ID
Source
Brief title
Condition
- Neurological disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Thermal pain (normal skin): Pain detection threshold (PDT);
Thermal pain (Ultraviolet (UVB) skin): Pain detection threshold (PDT);
Electrical Stair (pre-cold pressor): Pain tolerance threshold (PTT);
Pressure pain: Pain tolerance threshold (PTT);
Cold pressor: Pain tolerance threshold (PTT).
Secondary outcome
Electrical Stair (pre-cold pressor): Pain detection threshold (PDT), Area Under
the Visual Analogue Scale (VAS) pain Curve (AUC), and post-test VAS;
Electrical Stair (post-cold pressor): PDT, PTT, AUC, and post-test VAS;
Conditioned Pain Modulation Response (change from electrical stair pre- and
post- cold pressor): PDT, PTT, AUC;
Pressure Pain: PDT, AUC, and post-test VAS;
Cold pressor: PDT, AUC, and post-test VAS;
PF-05089771 plasma pharmacokinetic parameters: Cmax, AUClast, AUCinf , Tmax and
t* (if data permits);
Pregabalin and ibuprofen concentrations at the time of pharamcodynamic testing
from 0.5-10 hours;
Adverse events, laboratory safety, blood pressure, pulse rate, and
electrocardiogram (ECG).
Background summary
This is a study to investigate the effects of PF-05089771, a selective sodium
channel blocker (in this case the so-called Nav1.7 receptor), on a pain test
battery. It is expected that it has a profile suitable for the treatment of
chronic pain conditions.
Study objective
To investigate the ability of PF-05089771 to demonstrate analgesic properties
in healthy subjects for pre-specified primary endpoints using a panel of pain
tests.
Study design
This is a double blind, double dummy, single dose, randomized, 5-period
cross-over study. In this study PF-05089771 is the drug under investigation and
pregabalin and ibuprofen are used as positive controls. Twenty-five male
subjects, between 18 to 55 years of age, attend the clinic on 5 separate
occasions to examine the effects of PF-05089771 on evoked pain endpoints
included in the PainCart battery.
The study duration for a completed subject is a maximum of 8 weeks.
Intervention
PF-05089771 300 mg;
PF-05089771 300 mg in combination with pregabalin 300 mg;
Pregabalin 300 mg;
Ibuprofen 600 mg;
Placebo.
Study burden and risks
Based on our experiences in the FIH trials, no exceptional severe adverse drug
reactions are expected and burden/inconveniences for the subjects is considered
mild.
East 42nd Street 235
New York NY 10017
US
East 42nd Street 235
New York NY 10017
US
Listed location countries
Age
Inclusion criteria
1. Healthy males 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.
Exclusion criteria
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, 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 CHDR 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 study treatment or comparator drug or drugs of the same class, or any of the excipients.
16. Dark skin (Fitzpatrick skin type V or VI), widespread acne, tattoos or scarring on back.
17. Unwilling or unable to comply with the lifestyle guidelines described in this protocol.
18. Subjects who are investigational site staff members directly involved in the conduct of the study or their family members, site staff members otherwise supervised by the investigator, or subjects who are Pfizer employees directly involved in the conduct of the study.
19. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
Register | ID |
---|---|
EudraCT | EUCTR2014-004468-39-NL |
CCMO | NL51495.056.14 |
Other | to be listed on clinicaltrials.gov |