Safety And Efficacy Study Of Once Daily Controlled Release Pregabalin In The Treatment Of Patients With Postherpetic Neuralgia

Post Herpetic Neuralgia Clinical Trial

Official title:

A Phase 3 Double-blind, Randomized, Placebo-controlled, Safety And Efficacy Study Of Once Daily Controlled Release Pregabalin In The Treatment Of Patients With Postherpetic Neuralgia (Protocol A0081224)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01270828
• Other study ID #: A0081224
• Secondary ID: 2009-016766-86
• Status: Completed
• Phase: Phase 3
• Start date: March 2011
• Est. completion date: November 2014

Study information

• Verified date: December 2015
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to explore the safety and efficacy of a new once a day pregabalin formulation versus placebo for patients with post herpetic neuralgia (Shingles)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 806
• Est. completion date: November 2014
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients must have pain present for more than 3 months after the healing of the herpes zoster skin rash.

• At screening (V1) and enrollment (V2), patients must have a score of greater than or equal to 4 on the Pain Numeric Rating Scale (1 week recall period).

• At enrollment (V2), at least 4 pain diaries must be completed satisfactorily within the last 7 days and the average pain score must be greater than or equal to 4.

• Male or female of any race, at least 18 years of age, and using appropriate methods of contraception

Exclusion Criteria:

• Creatinine clearance <30 mL/min (estimated from serum creatinine).

• Skin conditions in the affected dermatome that could alter sensation

• Pregabalin use in the last 30 days. Subjects taking pregabalin in the last 30 days should be washed out of pregabalin for at least 30 days prior to screening visit. Patients who had not responded to pregabalin

Related Conditions & MeSH terms

• Neuralgia
• Neuralgia, Postherpetic
• Post Herpetic Neuralgia

Intervention

Drug:
• Pregabalin
Tablets, 82.5 to 660mg, once per day. Duration: 19 weeks
• placebo
Placebo, 82.5 to 660mg, once per day. Duration: 13 weeks

Locations

Country	Name	City	State
Bulgaria	DCC "St. Pantaleimon" OOD	Pleven
Bulgaria	MHAT-Pleven	Pleven
Bulgaria	MBAL "Tokuda Bolnitsa", Otdelenie po nevrologiya	Sofia
Bulgaria	MBALNP "Sveti Naum" EAD, Klinika po nervni bolesti za dvigatelni narushenia	Sofia
Bulgaria	Universitetska mnogoprofilna bolnitsa za aktivno lechenie Aleksandrovska, Klinika po Nevrologia	Sofia
Bulgaria	Vtora Mnogoprofilna Bolnitsa za Aktivno Lechenie ¿ Sofia, AD, Sofia, Nevrologichno otdelenie	Sofia
Colombia	Centro de Investigacion y Atencion Para la Salud Mental S.A. - CESAME	Bogota	Cundinamarca
Colombia	Fundacion Cardiovascular de Colombia	Floridablanca	Santander
Colombia	Reumalab S.A.S	Medellin	Antioquia
Croatia	Opca bolnica Karlovac	Karlovac	Karlovacka Županija
Croatia	Klinicki Bolnicki Centar Osijek	Osijek	Osjecko-baranjska Županija
Croatia	Opca bolnica "Dr. Ivo Pedisic"	Sisak	Sisacko-moslavacka Županija
Czechia	Neurologicka ambulance	Prerov I
Denmark	Aalborg Sygehus Nord	Aalborg	Region Nordjylland
Denmark	Glostrup Hospital	Glostrup
Germany	DGS-Schmerzzentrum Eichstätt	Eichstaett
Germany	Schmerzzentrum Frankfurt	Frankfurt/Main	Hessen
Germany	pro scientia med im MARE Klinikum	Kiel-Kronshagen	Schleswig-Holstein
Hong Kong	Family Medicine	Hong Kong
Hong Kong	Queen Elizabeth Hospital	Kowloon
India	M. S. Ramaiah Medical College and Hospitals	Bangalore	Karnataka
India	Manipal Hospital	Bangalore	Karnataka
India	Medanta Institute of Neurosciences	Gurgaon	Haryana
India	Mallikatta Neuro Centre	Mangalore	Karnataka
India	Indraprastha Apollo Hospitals	New Delhi
Poland	Niepubliczny Zaklad Opieki Zdrowotnej "Przychodnia Morena" Sp. z o.o.	Gdansk	Pomorskie
Poland	"SYNEXUS POLSKA" Sp. z o.o. Oddzial w Gdyni	Gdynia	Pomorskie
Poland	"SYNEXUS POLSKA" Sp. z o.o. Oddzial w Katowicach	Katowice	Slaskie
Poland	Prof. dr hab. med. Leszek Szepanski Prywatna Praktyka Lekarska Gabinet Reumatologiczny	Lublin	Lubelskie
Poland	"SYNEXUS POLSKA" Sp. z o.o. Oddzial w Warszawie	Warszawa	Mazowieckie
Poland	"SYNEXUS POLSKA" Sp. z o.o.	Wroclaw	Dolnoslaskie
Russian Federation	Kazan State Medical University	Kazan	Tatarstan, Respublika
Russian Federation	State Budgetary Educational Institution for higher Professional Training "Kazan State Medical Univer	Kazan	Tatarstan, Respublika
Russian Federation	GBUZ Nizhny Novgorod Regional Clinical Hospital N.A. Semashko	Nizhny Novgorod
Russian Federation	Clinic of Nervous Diseases M.I. Astvatsaturov	Saint-Petersburg
Russian Federation	St. Petersburg State Healthcare Institution City Hospital # 40 Kurortnogo Administrativnogo Rajona	Saint-Petersburg
Russian Federation	State Budgetary Educational Institution for Higher Professional Education	Smolensk
Russian Federation	State Budgetary Educational Institution for Higher Professional Education	Smolensk
Russian Federation	State Budgetary Health Institution of Yaroslavl region "Clinical hospital #10"	Yaroslavl
Serbia	Clinic for Neurology	Belgrade
Serbia	Clinic for Neurology	Nis
Slovakia	Euro-Neuro s.r.o., Neurologicka ambulancia	Bratislava
Slovakia	Univerzitna nemocnica Bratislava, Nemocnica sv. Cyrila a Metoda, Neurologicke oddelenie	Bratislava
Slovakia	MUDr. Eva Gasparova - neurologicka ambulancia	Hlohovec
Slovakia	Neurologicka ambulancia, Neuron-DT,s.r.o.	Zilina
South Africa	Iatros International	Bloemfontein
South Africa	Synapta Clinical Research Centre	Durban
South Africa	Mzansi Ethical Research Centre	Middelburg
South Africa	Nelson Mandela Academic Hospital Research Unit	Mthatha	Eastern Cape
South Africa	Jakaranda Pain Clinic	Pretoria
Sweden	CTC, Sahlgrenska sjukhuset/SU	Goteborg
Sweden	Me3plus Clinical Trials	Goteborg
Sweden	Probare	Lund	Skane Lan
Sweden	Center for Lakemedelsstudier	Malmo
Sweden	Bragee Medect AB	Stockholm
Taiwan	Chang Gung Medical Foundation-Linkou Branch	Kwei Shan Town	Taoyuan County
Taiwan	National Taiwan University Hospital (Neurology)	Taipei
Ukraine	Public Institution "Institute of Neurology, Psychiatry and Narcology of AMS of Ukraine"	Kharkiv
Ukraine	Kyiv City Clinical Hospital #4	Kyiv
Ukraine	Lviv NMU n.a. Danylo Galytskyy	Lviv
Ukraine	Regional Municipal Dermatovenerologic Dispensary	Lviv
Ukraine	Crimean Republican Institution "Clinical Dermatovenerologic Dispensary"	Simferopol
Ukraine	Municipal Establishment "Vinnitsa Regional Psychoneurological Hospital n.a. O.I. Yushchenko"	Vinnitsa
Ukraine	Municipal Establishment "City Clinical Hospital #2", Neurology Department	Zaporizhzhya
United States	Radiant Research	Akron	Ohio
United States	Albuquerque Clinical Trials, Inc.	Albuquerque	New Mexico
United States	Dent Neurological Institute	Amherst	New York
United States	Michigan Head Pain & Neurological Institute	Ann Arbor	Michigan
United States	Arlington Research Center, Inc.	Arlington	Texas
United States	Asheville Neurology Specialists, PA	Asheville	North Carolina
United States	JEM Research Institute	Atlantis	Florida
United States	Lovelace Scientific Resources, Inc.	Austin	Texas
United States	QUEST Research Institute	Bingham Farms	Michigan
United States	Millennium Pain Center, LLC	Bloomington	Illinois
United States	Injury Care Medical Center	Boise	Idaho
United States	Boston Clinical Trials	Boston	Massachusetts
United States	Orthopedic Research Institute	Boynton Beach	Florida
United States	Beacon Clinical Research	Brockton	Massachusetts
United States	SPRI Clinical Trials LLC	Brooklyn	New York
United States	Center for Clinical Research, Inc	Carmichael	California
United States	Radiant Research, Inc.	Chandler	Arizona
United States	Pharmacorp Clinical Trials, Inc.	Charleston	South Carolina
United States	(IP Shipping Address) Advocate Illinois Masonic Medical Center	Chicago	Illinois
United States	Chicago Anesthesia Pain Specialists	Chicago	Illinois
United States	Clinical Research of West Florida, Inc.	Clearwater	Florida
United States	Innovative Research of West Florida, Inc.	Clearwater	Florida
United States	Community Medical Providers	Clovis	California
United States	Sierra Medical Research	Clovis	California
United States	Inland Pain Medicine	Colton	California
United States	Radiant Research	Dallas	Texas
United States	Providence Health Partners-Center for Clinical Research	Dayton	Ohio
United States	Advanced Pain Care Clinic	Evansville	Indiana
United States	Clinical Research Advantage	Evansville	Indiana
United States	Global Scientific Innovations	Evansville	Indiana
United States	Clinical Physiology Associates	Fort Myers	Florida
United States	Fundamental Research	Gulf Shores	Alabama
United States	Health Care Family Rehab & Research Center	Hialeah	Florida
United States	The Center for Pharmaceutical Research, PC	Kansas City	Missouri
United States	Clinical Investigation Specialists, Inc.	Kenosha	Wisconsin
United States	Wells Institute for Health Awareness	Kettering	Ohio
United States	The Helm Center	Laguna Hills	California
United States	The Office of Dr. Stephen H. Miller, MD	Las Vegas	Nevada
United States	Lincoln Internal Medicine Associates	Lincoln	Nebraska
United States	Hearne Family Practice Clinic	Little Rock	Arkansas
United States	Larry Watkins, M.D. (Private Practice)	Little Rock	Arkansas
United States	Lynn Institute of the Ozarks	Little Rock	Arkansas
United States	University of Southern California	Los Angeles	California
United States	USC IDS Pharmacy	Los Angeles	California
United States	Montana Medical Research Inc	Missoula	Montana
United States	Clinical Trials of America, Inc.	Monroe	Louisiana
United States	Medex Healthcare Research, Inc - Saint Louis	New York	New York
United States	North American Partners In Pain Management	New York	New York
United States	Clinical Research Associates of Tidewater	Norfolk	Virginia
United States	Infinity Medical Research, Inc.	North Dartmouth	Massachusetts
United States	Translational Research Group, Inc	North Hollywood	California
United States	Laszlo Jozsef Mate, MD	North Palm Beach	Florida
United States	Family Care Specialists	Ocala	Florida
United States	Renstar Medical Research	Ocala	Florida
United States	Lynn Health Science Institute	Oklahoma City	Oklahoma
United States	Mark A Fisher	Oklahoma City	Oklahoma
United States	Drug Shipment Only: Heartland Clinical Research, Inc.	Omaha	Nebraska
United States	Heartland Clinical Research, Inc.	Omaha	Nebraska
United States	Compass Research, LLC	Orlando	Florida
United States	Elite Clinical Studies, LLC	Phoenix	Arizona
United States	HOPE Research Institute	Phoenix	Arizona
United States	The Pain Center of Arizona	Phoenix	Arizona
United States	The Pain Center of Arizona	Phoenix	Arizona
United States	Raleigh Neurology Associates, P.A.	Raleigh	North Carolina
United States	George J. Rederich, M.D., Incorporated	Redondo Beach	California
United States	ClinRx Research, LLC	Richardson	Texas
United States	Integrated Research Group, Inc.	Riverside	California
United States	Comprehensive Pain care of South Florida	Royal Palm Beach	Florida
United States	Medex Healthcare Research, Inc.	Saint Louis	Missouri
United States	Comprehensive Clinical Development Inc.	Saint Petersburg	Florida
United States	Drug Shipmnent Only Aristotelis T. Laliotis, M.D. Integrated Research Center, Inc.	San Diego	California
United States	Integrated Research Center, Inc.	San Diego	California
United States	Center For Clinical Research, Inc.	San Francisco	California
United States	Neurological Research Institute	Santa Monica	California
United States	Clinvest, A Division of Banyan Group, Inc	Springfield	Missouri
United States	Neurology Clinical Research, Inc.	Sunrise	Florida
United States	Clinical Research of West Florida, Inc.	Tampa	Florida
United States	Meridien Research	Tampa	Florida
United States	Genova Clinical Research	Tucson	Arizona
United States	Hillcrest Family Health Centers, Division of Clinical Research	Waco	Texas
United States	Foothills Pain Management Clinic, PS	West Covina	California
United States	The Center for Clinical Research	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

Countries where clinical trial is conducted

United States,  Bulgaria,  Colombia,  Croatia,  Czechia,  Denmark,  Germany,  Hong Kong,  India,  Poland,  Russian Federation,  Serbia,  Slovakia,  South Africa,  Sweden,  Taiwan,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Loss of Therapeutic Response.	Loss of Therapeutic Response (LTR) is defined as <30% pain response relative to the single blind phase baseline or patient discontinuation due to lack of efficacy or adverse events in the double blind phase of the study. For the calculation of <30% pain response relative to baseline, baseline will be defined as the mean of the last 7 observations prior to the start of SB treatment, which will be compared with the 7 days rolling average of pain response in DB phase. Participants may be discontinued due to lack of efficacy in this study at the discretion of the study physician.	13 Weeks
Secondary	Participants With Secondary LTR Based on 5 Day Rolling Average Diary Results	A secondary LTR endpoint (S-LTR) was defined as the 5 day rolling average pain score during DB, compared to the 5 day randomization baseline pain score. As a secondary endpoint, S-LTR was defined as: At least a 30% increase in the 5 days rolling average pain score during DB relative to the 5 Day randomization baseline pain score; A 5 days rolling average pain score =4. Participants who discontinue due to lack of efficacy or adverse events in the DB phase of the study will also be counted as an LTR.	13 Weeks
Secondary	Percentage of Participants With 30% Reduction in the Mean Pain Score.	The 30% pain responders were defined as participants with at least a 30% reduction in the mean pain score from SB baseline to DB endpoint.	13 Weeks
Secondary	Percentage of Participants With 50% Reduction in the Mean Pain Score.	The 50% pain responders were defined as participants with at least a 50% reduction in the mean pain score from SB baseline to DB endpoint.	13 Weeks
Secondary	Change From Baseline to Endpoint in Weekly Mean Pain Score.	The pain numeric rating scale (NRS Pain) consists of an 11 point NRS ranging from 0 (no pain) to 10 (worst possible pain). A rating of 1-3 is considered mild pain; 4-6, moderate pain; and 7-10, severe pain	SB Baseline (Enrollment) to Week 19 and DB Baseline (Week 6) to Week 19
Secondary	Change in the Weekly NRS-Pain (1-Week Recall).	The pain numeric rating scale (NRS Pain) consists of an 11 point NRS ranging from 0 (no pain) to 10 (worst possible pain). A rating of 1-3 is considered mild pain; 4-6, moderate pain; and 7-10, severe pain. Participants were asked to rate their pain over the past week.	SB Baseline (Enrollment) to Week 19 and DB Baseline (Week 6) to Week 19
Secondary	Change in the Medical Outcomes Study-Sleep Scale (MOS-SS).	The MOS-SS is a validated self administered questionnaire consisting of 12 items that assess key constructs of sleep. The scale has been found reliable and valid with good overall measurement properties. Instrument scoring yields 7 subscales (sleep disturbance, snoring, awaken short of breath or with a headache, quantity of sleep, optimal sleep, sleep adequacy, and somnolence) as well as a 9 item overall sleep problems index assessing sleep over the past week. Scores are transformed (actual raw score minus lowest possible score divided by possible raw score range multiplied by 100); total score range = 0 to 100; higher score indicates greater intensity of attribute.	SB Baseline (BL) (Enrollment) to Week 19 and DB Baseline (Week 6) to Week 19
Secondary	Change in the MOS-SS-Quantity of Sleep.	The MOS-SS is a validated self administered questionnaire consisting of 12 items that assess key constructs of sleep. The scale has been found reliable and valid with good overall measurement properties. Instrument scoring yields 7 subscales (sleep disturbance, snoring, awaken short of breath or with a headache, quantity of sleep, optimal sleep, sleep adequacy, and somnolence) as well as a 9 item overall sleep problems index assessing sleep over the past week.; The item "Quantity of sleep" of MOS-SS is presented here.	SB Baseline (BL) (Enrollment) to Week 19 and DB Baseline (Week 6) to Week 19
Secondary	The MOS-SS-Optimal Sleep.	The MOS-SS is a validated self administered questionnaire consisting of 12 items that assess key constructs of sleep. The scale has been found reliable and valid with good overall measurement properties. Instrument scoring yields 7 subscales (sleep disturbance, snoring, awaken short of breath or with a headache, quantity of sleep, optimal sleep, sleep adequacy, and somnolence) as well as a 9 item overall sleep problems index assessing sleep over the past week.; The optimal sleep score is a dichotomous 'Yes' or 'No' rating, where 'Yes' indicates optimal sleep (average 7-8 hours per night) and 'No' indicates not optimal sleep. The "percentage of participants with optimal sleep" is presented here.	Week 6 and Week 19
Secondary	Percentage of Participants With Change in the Patient Global Impression of Change (PGIC) Score	The PGIC is a participant-rated instrument that has been used in chronic pain and fibromyalgia studies to rate change in a patient's overall status. This single item instrument uses a 7 point Likert scale, anchored by (1) very much improved, to (7) very much worse.	Week 19
Secondary	Change in the Short Form 36 Health Survey (SF-36)	The SF 36 is a self administered, validated questionnaire that measures each of the following 8 health aspects: Physical functioning, role limitations due to physical problems, social functioning, bodily pain, mental health, role limitations due to emotional problems, vitality, and general health perception over the past week. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning) where, higher scores indicate a better health related quality of life.	Week 19
Secondary	Change in Mean Daily Sleep Interference Scores	The pain related sleep interference item rating scale is scored on an 11 point numeric rating scale (NRS Sleep). It is self administered by the subject in order to rate how pain has interfered with their sleep during the past 24 hours, ranging from 0 (pain does not interfere with sleep) to 10 (completely interferes (unable to sleep due to pain)). Participants are to describe how their pain has interfered with their sleep during the past 24 hours by choosing the appropriate number on the numeric rating scale.	Week 19
Secondary	Change in Hospital Anxiety and Depression Scales (HADS)	The HADS is a self administered questionnaire that was designed to screen for the presence of a mood disorder in medically ill patients. To distinguish psychiatric presentations from physical illness, the items focus on subjective disturbance of mood rather than physical signs. The HADS contains 14 items rated on 4 point Likert type scales. Two subscales assess depression and anxiety. Each subscale consists of 7 statements, rated on a scale of 0 to 3 (0 = No anxiety or depression, to 3 = Severe feelings of anxiety or depression). Separate scores are calculated for each subscale ranging from 0 to 21. Higher scores denote greater severity of depression or anxiety	Week 19
Secondary	Change in the Brief Pain Inventory (BPI-sf)	The BPI sf is a self-administered questionnaire developed to assess the severity of pain and the impact of pain on daily functions during a 24 hour period prior to evaluation. The BPI sf consists of 5 questions. Questions 1, 2, 3, and 4 measure pain on an 11 point scale from 0 (no pain) to 10 (worst pain possible). Question 5 consists of 7 item subsets which measure the level of interference of pain on daily functions on an 11 point scale from 0 (Does not interfere) to 10 (Completely interferes).	Week 19
Secondary	Percentage of Participants With Benefit From Treatment, Satisfaction With Treatment and Willingness to Continue Treatement (BSW)	The BSW is administered by the study physician or designated site personnel and consists of three single item measures designed to capture the patient's perception of the effect of treatment in terms of the relative benefit, their satisfaction, and their intention or willingness to continue on therapy.	Week 19
Secondary	Number of Participants With Adverse Events	An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. A serious adverse event is any untoward medical occurrence at any dose that: Results in death; Is life-threatening (immediate risk of death); Requires inpatient hospitalization or prolongation of existing hospitalization; Results in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); or Results in congenital anomaly/birth defect. The study physician used the adjective "severe" to those AEs that interfere significantly with participant's usual function.	Baseline to Week 20
Secondary	Percentage of Participants With Suicidal Behaviour/Ideation	Percentage of participants with suicidal behavior/ideation were noted as Baseline, Weeks 6, 11, 15, 19 and 20.	Baseline, Weeks 6, 11, 15, 19 and 20

External Links

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