A Study To Compare Pregabalin/PF-00489791 Combination Versus Pregabalin Alone In Post-Herpetic Neuralgia

A TWO WEEK DOUBLE-BLIND PLACEBO-CONTROLLED CROSSOVER STUDY TO COMPARE THE EFFICACY AND SAFETY OF A PREGABALIN/PF-00489791 COMBINATION VERSUS PREGABALIN ALONE IN PATIENTS WITH POST-HERPETIC NEURALGIA

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00599638

Enrollment

Registered

2008-01-24

Start date

2008-04-09

Completion date

2008-12-23

Last updated

2021-08-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Postherpetic Neuralgia

Brief summary

Pregabalin is an alpha-2 delta ligand approved for the treatment of neuropathic pain, however, not all patients will respond to this drug. This study will compare the efficacy of pregabalin when administered with an experimental drug PF-00489791, in patients with post-herpetic neuralgia. The efficacy of this combination will be compared to pregabalin alone.

Interventions

DRUGpregabalin

75mg bid titrating to 150mg bid on day 4

DRUGpregabalin/PF-00489791

Pregabalin 75mg bid titrating to 150mg bid on day 4; PF-00489791: 4mg od titrating to 10mg od on day 4

DRUGPlacebo

Placebo

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Male or female of non-childbearing potential * Pain present for more than 3 months after healing of herpes zoster skin rash * VAS score of \>=40mm at screening and baseline visits

Exclusion criteria

* Patients with pain conditions which might impair the assessment of postherpetic neuralgia * Skin conditions in the affected dermatome that could alter sensation other than postherpetic neuralgia * History or diagnosis of DSM IV major depressive disorder

Design outcomes

Primary

Measure	Time frame	Description
Mean Pain Score on Daily Pain Rating Scale (DPRS)	End of treatment period (included both Week 2 and Week 6)	Pain was assessed by using a daily pain rating scale that consisted of an 11-point numeric scale ranging from 0 (no pain) to 10 (worst possible pain), higher scores indicate more pain intensity. Participants described their pain during the past 24 hours by choosing the appropriate number between 0 and 10. Self-assessment was performed daily. The mean pain score was defined as the mean of the last 7 daily pain ratings scale scores while taking study medication, at end of each treatment period: Period 1 (Week 2) and Period 2 (Week 6), respectively. Mean pain score had a score range of 0 (no pain) to 10 (worst possible pain), higher scores indicate more pain. Cumulative data of mean pain scores at end of treatment for both the periods was calculated and reported in terms of adjusted mean and standard error.

Secondary

Measure	Time frame	Description
Pain Visual Analogue Scale (VAS) at Baseline and Week 4	Baseline, Week 4	Participants marked intensity of the pain on a scale, ranging from 0 millimeters (mm) = no pain to 100 mm = worst possible pain, where higher scores indicate more pain.
Neuropathic Pain Symptom Inventory (NPSI)	End of treatment period (included both Week 2 and Week 6)	Participant rated 10-item questionnaire to evaluate different symptoms of neuropathic pain (spontaneous pain like \[item 1 to 3\]: burning, squeezing, pressure; painful attack like \[item 4 to 5\]: electric shock, stabbing; pain provoked on \[item 6 to 8\]: light touching, pressure, contact with something cold; abnormal sensations like \[item 9 to 10\]: pins and needles, tingling). Each item was rated on an 11-point numerical scale range: 0 (absence of pain) to 10 (maximum intensity of pain). Total NPSI scale ranged from 0 (no pain) to 100 (maximum pain). Higher scores indicate a greater intensity of pain. Cumulative data of NPSI scale at end of treatment for both the periods (Period 1 \[Week 2\] and Period 2 \[Week 6\]) was calculated and reported in terms of adjusted mean and standard error.
Number of Participants With Clinically Significant Vital Signs Abnormalities	Baseline up to Week 7	Vital signs abnormalities included sitting, standing: systolic, diastolic blood pressure and heart rate. Clinical significance was judged by investigator.
Percentage of Participants With Patient Global Impression of Change (PGIC) Score	End of treatment period (included both Week 2 and Week 6)	The PGIC is a participant-rated instrument that measures change in the participants' overall status on a 7-point scale. Scores range from 1 (very much improved) to 7 (very much worse), lower scores indicated more improvement. PGIC was evaluated using 3 categories: improvement (scores 1-3), no change (score 4), and worsening (scores 5-7). In this outcome measure percentage of participants with categories: improved, no change and worsening, based on PGIC score were reported. Cumulative data at end of treatment for both the periods (Period 1 \[Week 2\] and Period 2 \[Week6\]) was calculated and reported.
Number of Participants With Clinically Significant Laboratory Abnormalities: Hematology	Baseline up to Week 7	Criteria for hematology abnormalities included Hemoglobin: \<0.8\lower limit of normal (LLN) and hematocrit: \<0.8\LLN. Clinical significance was judged by investigator.
Number of Participants With Clinically Significant Laboratory Abnormalities: Clinical Chemistry	Baseline up to Week 7	Criteria for clinical chemistry abnormalities included total bilirubin: greater than (\>) 1.5\upper limit of normal (ULN); aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase: \>3.0\ULN; total protein, albumin: \<0.8\LLN or \>1.2\ULN; blood urea nitrogen, creatinine: \>1.3\ULN; uric acid: \>1.2\ULN; sodium: \<0.95\LLN or \>1.05\ULN; potassium, chloride, calcium: \<0.9\LLN or \>1.1\ULN; creatine kinase: \>2.0\*ULN. Clinical significance was judged by investigator.
Number of Participants With Clinically Significant Laboratory Abnormalities: Urinalysis	Baseline up to Week 7	Urinalysis abnormalities criteria included: urine specific gravity: \<1.003 to \>1.030; urine pH: \<4.5 to \>8; urine glucose, urine ketones, urine proteins, urine blood/hemoglobin: \>=1. Clinical significance was judged by investigator.
Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities	Baseline up to Week 7	Criteria for ECG abnormalities: Maximum QTc (corrected QT) interval, QTcB (Bazett's correction formula) and QTcF (Fridericia's correction formula): 450 to less than (\<) 480 milliseconds (msec), 480 to \<500 msec and greater than equal to (\>=) 500 msec; Maximum QTc interval increase from baseline: \>=30 to \<60 and \>=60 (msec); PR interval: \>=300 msec and percent change \>=25 or 50 percent; QRS complex: percent change \>=25 or 50 percent. Clinical significance was judged by investigator.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Pregabalin Then Placebo Participants received 75 milligram (mg) capsule of Pregabalin orally twice daily from Day 1 to Day 3 and 150 mg capsule of Pregabalin orally twice daily from Day 4 to Day 14 in first intervention period followed by placebo matched to Pregabalin twice daily from Day 1 to Day 14 in second intervention period. A washout period of at least 14 days was maintained between each intervention period. Participants had follow up of 1 week.	16
Placebo Then Pregabalin Participants received placebo matched to Pregabalin twice daily from Day 1 to Day 14 in first intervention period followed by Pregabalin 75 mg capsule orally twice daily from Day 1 to Day 3 and 150 mg capsule of Pregabalin orally twice daily from Day 4 to Day 14 in second intervention period. A washout period of at least 14 days was maintained between each intervention period. Participants had follow up of 1 week.	13
Pregabalin + Placebo Then Pregabalin + PF-00489791 Participants received 75 mg capsule of Pregabalin orally twice daily from Day 1 to Day 3 and 150 mg capsule of Pregabalin orally twice daily from Day 4 to Day 14 along with placebo matched to PF-00489791 orally once daily from Day 1 to Day 14 in first intervention period. In second intervention period participants received 75 mg capsule of Pregabalin orally twice daily from Day 1 to Day 3 and 150 mg capsule of Pregabalin orally twice daily from Day 4 to Day 14 along with two tablets of 2 mg PF-00489791 orally once daily from Day 1 to Day 3 and 10 mg tablet of PF-00489791 orally once daily from Day 4 to Day 14. A washout period of at least 14 days was maintained between each intervention period. Participants had follow up of 1 week.	20
Pregabalin + PF-00489791 Then Pregabalin + Placebo Participants received 75 mg capsule of Pregabalin orally twice daily from Day 1 to Day 3 and 150 mg capsule of Pregabalin orally twice daily from Day 4 to Day 14 along with two tablets of 2 mg PF-00489791 orally once daily from Day 1 to Day 3 and 10 mg tablet of PF-00489791 orally once daily from Day 4 to Day 14 in first intervention period. In second intervention period participants received 75 mg capsule of Pregabalin orally twice daily from Day 1 to Day 3 and 150 mg capsule of Pregabalin orally twice daily from Day 4 to Day 14 along with a placebo matched to PF-00489791 orally once daily from Day 1 to Day 14. A washout period of at least 14 days was maintained between each intervention period. Participants had follow up of 1 week.	21
Total	70

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003
First Intervention Period (2 Weeks)	Adverse Event	1	0	3	2
First Intervention Period (2 Weeks)	Protocol Violation	0	1	0	1
First Intervention Period (2 Weeks)	Randomized but not Treated	0	1	0	1
First Intervention Period (2 Weeks)	Withdrawal by Subject	1	0	0	1
Second Intervention Period (2 Weeks)	Protocol Violation	1	0	0	0
Washout Period (2 Weeks)	Adverse Event	0	0	0	1
Washout Period (2 Weeks)	Lost to Follow-up	0	0	0	1
Washout Period (2 Weeks)	Protocol Violation	0	1	0	0
Washout Period (2 Weeks)	Withdrawal by Subject	1	0	0	1

Baseline characteristics

Characteristic	Pregabalin Then Placebo	Placebo Then Pregabalin	Pregabalin + Placebo Then Pregabalin + PF-00489791	Pregabalin + PF-00489791 Then Pregabalin + Placebo	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	9 Participants	5 Participants	15 Participants	14 Participants	43 Participants
Age, Categorical Between 18 and 65 years	7 Participants	8 Participants	5 Participants	7 Participants	27 Participants
Sex: Female, Male Female	8 Participants	8 Participants	13 Participants	14 Participants	43 Participants
Sex: Female, Male Male	8 Participants	5 Participants	7 Participants	7 Participants	27 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	22 / 38	35 / 61	7 / 26
serious Total, serious adverse events	1 / 38	0 / 61	0 / 26

Outcome results

Primary

Mean Pain Score on Daily Pain Rating Scale (DPRS)

Pain was assessed by using a daily pain rating scale that consisted of an 11-point numeric scale ranging from 0 (no pain) to 10 (worst possible pain), higher scores indicate more pain intensity. Participants described their pain during the past 24 hours by choosing the appropriate number between 0 and 10. Self-assessment was performed daily. The mean pain score was defined as the mean of the last 7 daily pain ratings scale scores while taking study medication, at end of each treatment period: Period 1 (Week 2) and Period 2 (Week 6), respectively. Mean pain score had a score range of 0 (no pain) to 10 (worst possible pain), higher scores indicate more pain. Cumulative data of mean pain scores at end of treatment for both the periods was calculated and reported in terms of adjusted mean and standard error.

Time frame: End of treatment period (included both Week 2 and Week 6)

Population: Full analysis set included all participants who were randomized and had received at least 1 dose of study drug, regardless of whether they had efficacy data and did not have any significant protocol violation. Here, Overall Number of Participants Analyzed signifies participants who were evaluable for this outcome measure.

Arm	Measure	Value (MEAN)	Dispersion
Pregabalin + PF-00489791	Mean Pain Score on Daily Pain Rating Scale (DPRS)	4.32 units on a scale	Standard Error 0.343
Pregabalin	Mean Pain Score on Daily Pain Rating Scale (DPRS)	4.22 units on a scale	Standard Error 0.253
Placebo	Mean Pain Score on Daily Pain Rating Scale (DPRS)	5.57 units on a scale	Standard Error 0.451

p-value: 0.39180% CI: [-0.31, 0.48]Mixed Models Analysis

p-value: 0.000280% CI: [-1.78, -0.86]Mixed Models Analysis

Secondary

Neuropathic Pain Symptom Inventory (NPSI)

Participant rated 10-item questionnaire to evaluate different symptoms of neuropathic pain (spontaneous pain like \[item 1 to 3\]: burning, squeezing, pressure; painful attack like \[item 4 to 5\]: electric shock, stabbing; pain provoked on \[item 6 to 8\]: light touching, pressure, contact with something cold; abnormal sensations like \[item 9 to 10\]: pins and needles, tingling). Each item was rated on an 11-point numerical scale range: 0 (absence of pain) to 10 (maximum intensity of pain). Total NPSI scale ranged from 0 (no pain) to 100 (maximum pain). Higher scores indicate a greater intensity of pain. Cumulative data of NPSI scale at end of treatment for both the periods (Period 1 \[Week 2\] and Period 2 \[Week 6\]) was calculated and reported in terms of adjusted mean and standard error.

Time frame: End of treatment period (included both Week 2 and Week 6)

Arm	Measure	Value (MEAN)	Dispersion
Pregabalin + PF-00489791	Neuropathic Pain Symptom Inventory (NPSI)	25.71 units on a scale	Standard Error 3.134
Pregabalin	Neuropathic Pain Symptom Inventory (NPSI)	25.87 units on a scale	Standard Error 2.168
Placebo	Neuropathic Pain Symptom Inventory (NPSI)	35.25 units on a scale	Standard Error 5.148

p-value: 0.33880% CI: [-2.47, 4.84]Mixed Models Analysis

p-value: 0.002280% CI: [-13.89, -5.42]Mixed Models Analysis

Secondary

Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities

Criteria for ECG abnormalities: Maximum QTc (corrected QT) interval, QTcB (Bazett's correction formula) and QTcF (Fridericia's correction formula): 450 to less than (\<) 480 milliseconds (msec), 480 to \<500 msec and greater than equal to (\>=) 500 msec; Maximum QTc interval increase from baseline: \>=30 to \<60 and \>=60 (msec); PR interval: \>=300 msec and percent change \>=25 or 50 percent; QRS complex: percent change \>=25 or 50 percent. Clinical significance was judged by investigator.