Clinical trial NCT01058642: Study to Assess the Efficacy, Safety, and Tolerability of ADL5747 in Participants With Postherpetic Neuralgia
Official title: A Phase 2A, Randomized, Blinded, Placebo- and Active-controlled, 2-Period Crossover Study to Assess the Analgesic Efficacy, Safety, and Tolerability of ADL5747 in Subjects With Postherpetic Neuralgia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Postherpetic Neuralgia
Keywords: pain
delta opioid receptor agonist
Lead sponsor: Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Sponsor class: INDUSTRY
Collaborators: name: Pfizer
First posted: 2010-01-29
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The primary purpose of this study is to evaluate the analgesic efficacy of ADL5747 in participants with postherpetic neuralgia (PHN). The secondary objective of this study is to evaluate the safety, tolerability, and pharmacokinetics of ADL5747.


Eligibility criteria: Key inclusion Criteria:

* have a diagnosis of PHN (defined as pain present for at least 3 months after the healing of herpes zoster rash; there is no upper limit on the duration of PHN)
* have an average daily pain score of at least 4 on the numeric pain rating scale (0-10) at the start of baseline week for Treatment Period 1 (Day -7) through the start of the first week of Treatment Period 1 (Day 1)
* be willing and able to understand and comply with protocol requirements, dietary and dosing regimens, and other protocol instructions and restrictions (for example, forgo use of their normal pain medication and other protocol specified prohibited medications for the duration of the study)
* for male participants, be surgically sterile or agree to use an appropriate method of contraception or have a sexual partner who is surgically sterile or using an insertable, injectable, transdermal, or combination oral contraceptive approved and deemed highly effective by the United States Food and Drug Administration (FDA) from the first dose of study medication through 30 days after the last dose of study medication on Day 49
* for female participants of childbearing potential, be using an insertable, injectable, transdermal, or combination oral contraceptive approved and deemed highly effective by the FDA from the first dose of study medication through 30 days after the last dose of study medication on Day 49 and have negative results on a serum pregnancy test during the start of the screening period to obtain informed consent and determine eligibility for the study (Day -37 to -14) and on a urine pregnancy test during the start of the first week of Treatment Period 1 (Day 1) (women who are surgically sterile \[for example, hysterectomy, tubal ligation\] or postmenopausal \[if ≥ 55 years old, no menses for at least 2 years; if \< 55 years old, follicle stimulating hormone concentrations within the postmenopausal range of \> 40 milli-International Units per milliliter (mIU/mL) and 17 β estradiol levels of \< 37 picograms per milliliter (pg/mL)\] are also eligible to participate)

Key Exclusion Criteria:

* be pregnant or lactating
* have significant skin lesions that could interfere with pain assessment
* have a history of seizures or a history of abnormal electroencephalographic results at any time (participants with a history of febrile seizures before the age of 6 years may be enrolled)
* have had previous neurolytic or neurosurgical therapy for PHN
* have had a treatment that included local anesthetic nerve blocks within 30 days before the start of the baseline week for Treatment Period 1 (Day -7)
* have any other type of pain that may impair the self-assessment of pain due to PHN
* have, as determined by the investigator or the sponsor's medical monitor, a history or clinical manifestations of significant renal, hepatic, hematologic, cardiovascular, metabolic, gastrointestinal, neurologic, psychiatric, or other condition that would preclude participation in the study
* have an active malignancy of any type (participants with a history of successfully treated malignancy \> 5 years before the scheduled first dose of study medication and participants with treated basal or squamous cell cancer may be enrolled)
* have a medical history or condition that may interfere with drug absorption (for example, stomach resection)
* be currently using protocol specified prohibited medications in the absence of appropriate washout
* be currently taking moderate or strong inhibitors or inducers of cytochrome P450-3A (CYP3A) or inhibitors of P glycoprotein transporters
* have an estimated glomerular filtration rate (GFR) that is less than or equal to 60 mL/min calculated by the Cockcroft Gault equation or have alanine aminotransferase and/or aspartate aminotransferase levels that are at least 2 times the upper limit of normal
* have a history of substance abuse or dependence within the previous 5 years, including alcohol or positive results on the urine drug screen at start of screening period, start of baseline week, or start of the first week of Treatment Period 1 (Day -37 to Day 1); participants may be enrolled if positive results are due to medication(s) prescribed for the participant and permitted by the protocol
* have a history of suicide attempts or be judged clinically to be at serious risk of suicide
* have a score of more than 29 on the Beck Depression Inventory-II at start of screening period (Day -37 to Day -14)
* have a history of allergy to acetaminophen (the rescue medication for this study)
* have a history of intolerance to pregabalin or documented failure to respond to a maximally tolerated dose of pregabalin
* have ever received the investigational drug ADL5747 or have participated in any clinical study involving an investigational product in which they received that product within 30 days before the scheduled administration of study medication for this study

Primary outcomes:
measure: Change in Weekly Average Numeric Pain Rating Scale (NPRS) Score From Baseline to End of Treatment (Week 2 of Each Treatment Period)
timeFrame: Baseline, Week 2 of Treatment Period 1 or 2
Secondary outcomes:
Other outcomes:
Locations:
city: West Palm Beach
country: United States
facility: Laszlo J. Mate, MD
state: Florida
Study officials:
affiliation: Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
name: Wei Du, MD
role: STUDY_DIRECTOR
References: