Clinical trial NCT00488839: IPX056 in Subjects With Established Spasticity Resulting From Multiple Sclerosis
Official title: A Double-Blind, Randomized, Placebo- and Active Comparator- Controlled, Parallel Group, Multinational Study to Evaluate the PK and PD of IPX056 in Subjects With Established Spasticity Resulting From Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Sclerosis
Keywords: Spasticity
Multiple Sclerosis
Lead sponsor: Impax Laboratories, LLC
Sponsor class: INDUSTRY
First posted: 2007-06-20
Enrollment: 173
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the effects, both good and bad, of IPX056 on subjects and their spasticity. This study will also determine the relationship between the amount of IPX056 in blood and the effects on spasticity. Lastly, this study will determine how long IPX056 affects spasticity.

Detailed description: The primary objective of this study is to demonstrate that IPX056 reduces spasticity, measured by Ashworth score, in subjects with multiple sclerosis (MS). This study will also (1) assess the correlation between pharmacokinetic (PK) and pharmacodynamic (PD) endpoints (Ashworth score), and (2) quantify the duration of pharmacodynamic effects for IPX056 as well as marketed baclofen tablet in subjects with Multiple Sclerosis (MS) after a single dose. Additionally, the efficacy parameters, including Multiple Sclerosis Impact Scale (MSIS)-29, spasm frequency and nighttime awakening score, spasticity control, morning stiffness, and Global Assessment of Efficacy and Tolerability, will be assessed during open-label extension period. The safety of IPX056 will be monitored throughout the study.

This study consists of 2 parts: Part I (Screening Visit \& Visit 1) of the study is a single-dose, double-blind, randomized, placebo- and active comparator-controlled, parallel group design containing a single 12 hour PK/PD evaluation period. Part II is an optional, approximately 9-week open-label extension study and will start during Visit 1, immediately after Visit 1 PK/PD procedures are completed.

Eligibility criteria: Inclusion Criteria:

* Male or female at least 18 years old. If female and of childbearing potential, continuing to practice and willing to continue throughout the study with appropriate contraceptives (defined as oral, injected, or implanted contraceptives, or barrier contraception). The subject must agree to take every precaution to ensure that pregnancy will not occur during the study. Female subjects of childbearing potential must have a negative urine pregnancy test immediately prior to study entry.
* Able to understand and willing to voluntarily sign an informed consent form (ICF) and an Authorization to Use and Disclose Protected Health Information form (as required by the Health Insurance Portability and Accountability Act {HIPAA} legislation, if appropriate for the region) prior to the performance of any study-specific procedures.
* Has a negative urine drug screen at screening visit.
* Has Definite multiple sclerosis by Poser or McDonald Criteria.
* Expanded Disability Status Scale (EDSS) rating between 3.0-8.0
* Has a normal ECG and a blood pressure \<160/95 mmHg (systolic)/diastolic) at screening, measured in the sitting position after approximately 5 minutes of quiet rest.
* If the subject has a history of or presence of clinically significant peptic ulcers, liver disease, diabetes mellitus, hypertension or heart disease, the subject must be on a stable treatment regimen for a minimum of 3 months prior to Screening Visit
* Wiling to wash out current medication with anti-spasticity activities, including but not limited to baclofen, benzodiazepines, clonazepam, clonidine, dantrolene, diazepam, gabapentin, and tizanidine.
* Ashworth score of 2 or more for at least one of the three lower extremity muscle groups (hip adductor, knee flexor, knee extensor) in the most affected limb and a total minimum score of 6 for four muscle groups (the above three plus plantar flexor) on both limbs (maximum total score is 32) during screening visit and at pre-dose during PK/PD Visit 1.
* Able and willing to comply with the protocol, including availability for all scheduled clinic visits

Exclusion Criteria:

* If female, the subject is:

  1. pregnant; or planning to become pregnant; or
  2. breastfeeding; or
  3. a woman of child-bearing potential (defined as post menarche and biologically capable of becoming pregnant \[i.e., not surgically sterile\]) who is engaged in active heterosexual relations and is not using a barrier or hormonal form of birth control (i.e. oral, injected, or implanted contraceptives).
* History of allergic or severe intolerance to baclofen.
* Did not respond to previous baclofen treatment in any formulation.
* Treated with intrathecal baclofen within the previous 6 months prior to the Screening Visit.
* Has experienced an exacerbation of MS within 6 months prior to the Screening Visit.
* Symptomatic urinary tract infection (UTI) within 4 weeks prior to the Screening Visit and more than two (2) UTI incidents within the last 6 months.
* Serum creatinine level ≥ 2 x ULN (upper limit of normal reference range) at the Screening Visit or requires dialysis.
* Liver enzyme values ≥ 2 x ULN (upper limit of normal reference range) at the Screening Visit.
* Uncontrolled peptic ulcers, liver disease, diabetes mellitus, bladder sphincter hypertonia, hypertension or heart disease.
* History of seizure or epilepsy, or is currently taking an anti-convulsant for treatment or control of seizure.
* Concomitant neurologic conditions causing spasticity (e.g. stroke, cerebral palsy, traumatic brain injury) or rigidity (e.g. Parkinson's disease).
* Any medical condition, including psychiatric disease, which would interfere with the interpretation of the study results, the conduct of the study, or the safety of the subject.
* Currently taking antipsychotics, CNS depressants or CNS depression producing medications (including alcohol, sedating antihistamines, barbiturates, narcotics, and phenothiazines), monoamine oxidase inhibitors (MAOI, including furazolidone, procarbazine, selegiline, and tranylcypromine), and tricyclics.
* Unable or unwilling to wash out current anti-spasticity medications, including but not limited to baclofen, benzodiazepines, clonazepam, clonidine, dantrolene, diazepam, gabapentin, and/or tizanidine for Day 1, Visit 1, procedures. However, these medications will be allowed during open label study.
* Unable or unwilling to participate 12-hour PK/PD procedures during Visit 1.
* Treated with Botulinum Toxin Type A or B within the previous 6 months, or Phenol or therapeutic alcohol nerve block within 12 months prior to the Screening Visit.
* History of alcohol abuse or use of recreational drugs within 12 months prior to the Screening Visit.
* Has received an investigational drug or device within 30 days prior to the Screening Visit.
* Has clinically significant limitation of passive range of motion around any of the joints being assessed in this study.
* Has had major surgery within 3 months prior to Screening visit that may affect spasticity assessments such as abdominal surgery, back surgery, lower leg and knee surgeries.

Primary outcomes:
measure: Overall mean changes from predose (baseline) in total Ashworth scores of the four lower extremity muscle groups (hip adductors, knee flexors, knee extensors, and plantar flexors) of both lower limbs over 12 hours assessed hourly after dosing
timeFrame: 12 hours
Secondary outcomes:
measure: Duration of effect (improvement in Ashworth Scale) for IPX056
timeFrame: 12 hours
measure: Establishment of relationships between baclofen plasma concentration with improvement in Ashworth Scale
timeFrame: 12 hours
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Northwest NeuroSpecialists
state: Arizona
city: Little Rock
country: United States
facility: OrthoArkansas, P. A.
state: Arkansas
city: Little Rock
country: United States
facility: OrthoArkansas, P.A.
state: Arkansas
city: Colorado Springs
country: United States
facility: Patricia Fodor
state: Colorado
city: Hollywood
country: United States
facility: Sunrise Clinical Research
state: Florida
city: Tampa
country: United States
facility: Meridien Research
state: Florida
city: Atlanta
country: United States
facility: MS Center of Atlanta
state: Georgia
city: Peoria
country: United States
facility: OSF Saint Francis Medical Center
state: Illinois
city: Elkhart
country: United States
facility: Elkhardt Clinic
state: Indiana
city: Lenexa
country: United States
facility: MidAmerica Neuroscience Institute
state: Kansas
city: Springfield
country: United States
facility: Springfield Neurology
state: Massachusetts
city: Ann Arbor
country: United States
facility: General Clinical Research Center 7A
state: Michigan
city: Saint Louis
country: United States
facility: Medex Healthcare Research, Inc.
state: Michigan
city: Traverse City
country: United States
facility: Northern Michigan Neurology
state: Michigan
city: Mineola
country: United States
facility: Winthrop University Hospital
state: New York
city: Upland
country: United States
facility: Crozer Chester Medical Center
state: Pennsylvania
city: Lubbock
country: United States
facility: Bhupesh Dihenia
state: Texas
city: San Antonio
country: United States
facility: Integra Clinical Research
state: Texas
city: Bennington
country: United States
facility: Neurological Research Center
state: Vermont
city: Richmond
country: United States
facility: Virginia Commonwealth University Medical Center
state: Virginia
city: Montreal
country: Canada
facility: Montreal Neurological Institute and Hospital
state: Quebec
city: Calgary
country: Canada
facility: Foothills Medical Centre, MS Clinic, SSB
city: Tallinn
country: Estonia
facility: West-Tallinn Central Hospital
city: Riga
country: Latvia
facility: Vecmilgravis Hospital, Latvian Maritime Medicine Center
city: Chernihiv
country: Ukraine
facility: Chernihiv Regional Hospital Department of Neurology
city: Dnipropetrovsk
country: Ukraine
facility: Neurology and Neurosurgery Dpt., Postgraduation training faculty, Dnipropetrovsk State medical Academy
city: Kharkiv
country: Ukraine
facility: Institue of Neruology, Psychiatry and Narcology of AMS of Ukraine
city: Kyiv
country: Ukraine
facility: Department of nervous system demyelization diseases of City Clinical Hospital
city: Odessa
country: Ukraine
facility: Odessa Regional Clinical Hospital
city: Poltava
country: Ukraine
facility: Neurology department of Ukraine medical stomatological akademy
city: Vinnytsya
country: Ukraine
facility: Vinnytsya Regional Psychoneurological Hospital
Study officials:
affiliation: Impax Laboratories, LLC
name: Impax Study Director
role: STUDY_DIRECTOR
References: