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IPX056 in Subjects With Established Spasticity Resulting From Multiple Sclerosis

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00488839
First Posted: June 20, 2007
Last Update Posted: February 13, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
IMPAX Laboratories, Inc.
  Purpose
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.

Condition Intervention Phase
Multiple Sclerosis Drug: IPX056 20 mg Drug: IPX056 40 mg Drug: Encapsulated Baclofen 20 mg Drug: Placebo Baclofen Tablet Drug: IPX056 10 mg Drug: IPX056 30 mg Drug: IPX056 35 mg Drug: Placebo IPX056 20 mg Drug: Placebo IPX056 40 mg Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by IMPAX Laboratories, Inc.:

Primary Outcome Measures:
  • 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 [ Time Frame: 12 hours ]

Secondary Outcome Measures:
  • Duration of effect (improvement in Ashworth Scale) for IPX056 [ Time Frame: 12 hours ]
  • Establishment of relationships between baclofen plasma concentration with improvement in Ashworth Scale [ Time Frame: 12 hours ]

Enrollment: 173
Study Start Date: June 2007
Study Completion Date: May 2008
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
IPX056 20 mg - OLE
A single dose of IPX056 20 mg, Placebo IPX056 40 mg and Placebo Baclofen Tablet (Part 1), 9 week Open label extension of IPX056 (flexible dose design, IPX056 10 mg, IPX056 20 mg, IPX056 30 mg, IPX056 35 mg, or IPX056 40 mg)
Drug: IPX056 20 mg
IPX056 Extended Release capsule containing 20 mg baclofen
Other Name: Baclofen ER 20 mg
Drug: IPX056 40 mg
IPX056 Extended Release capsule containing 40 mg baclofen
Other Name: Baclofen ER 40 mg
Drug: Encapsulated Baclofen 20 mg
Baclofen 20mg tablet was encapsulated for blinding.
Other Name: Active comparator
Drug: Placebo Baclofen Tablet
Placebo capsule encapsulated placebo Baclofen tablet
Drug: IPX056 10 mg
IPX056 Extended Release capsule containing 10 mg baclofen
Other Name: Baclofen ER 10 mg
Drug: IPX056 30 mg
IPX056 Extended Release capsule containing 30 mg baclofen
Other Name: Baclofen ER 30 mg
Drug: IPX056 35 mg
IPX056 Extended Release capsule containing 35 mg baclofen
Other Name: Baclofen ER 35 mg
Drug: Placebo IPX056 40 mg
Placebo capsule for IPX056 40 mg
IPX056 40 mg - OLE
A single dose of IPX056 40 mg, Placebo IPX056 20 mg and Placebo Baclofen Tablet (Part 1), 9 week Open label extension of IPX056 (flexible dose design, IPX056 10 mg, IPX056 20 mg, IPX056 30 mg, IPX056 35 mg, or IPX056 40 mg)
Drug: IPX056 20 mg
IPX056 Extended Release capsule containing 20 mg baclofen
Other Name: Baclofen ER 20 mg
Drug: IPX056 40 mg
IPX056 Extended Release capsule containing 40 mg baclofen
Other Name: Baclofen ER 40 mg
Drug: Encapsulated Baclofen 20 mg
Baclofen 20mg tablet was encapsulated for blinding.
Other Name: Active comparator
Drug: Placebo Baclofen Tablet
Placebo capsule encapsulated placebo Baclofen tablet
Drug: IPX056 10 mg
IPX056 Extended Release capsule containing 10 mg baclofen
Other Name: Baclofen ER 10 mg
Drug: IPX056 30 mg
IPX056 Extended Release capsule containing 30 mg baclofen
Other Name: Baclofen ER 30 mg
Drug: IPX056 35 mg
IPX056 Extended Release capsule containing 35 mg baclofen
Other Name: Baclofen ER 35 mg
Drug: Placebo IPX056 20 mg
Placebo capsule for IPX056 20 mg
Baclofen 20 mg - OLE
A single dose of Encapsulated Baclofen 20 mg, Placebo IPX056 20 mg and Placebo IPX056 40 mg (Part 1), 9 week Open label extension of IPX056 (flexible dose design, IPX056 10 mg, IPX056 20 mg, IPX056 30 mg, IPX056 35 mg, or IPX056 40 mg)
Drug: IPX056 20 mg
IPX056 Extended Release capsule containing 20 mg baclofen
Other Name: Baclofen ER 20 mg
Drug: IPX056 40 mg
IPX056 Extended Release capsule containing 40 mg baclofen
Other Name: Baclofen ER 40 mg
Drug: Encapsulated Baclofen 20 mg
Baclofen 20mg tablet was encapsulated for blinding.
Other Name: Active comparator
Drug: IPX056 10 mg
IPX056 Extended Release capsule containing 10 mg baclofen
Other Name: Baclofen ER 10 mg
Drug: IPX056 30 mg
IPX056 Extended Release capsule containing 30 mg baclofen
Other Name: Baclofen ER 30 mg
Drug: IPX056 35 mg
IPX056 Extended Release capsule containing 35 mg baclofen
Other Name: Baclofen ER 35 mg
Drug: Placebo IPX056 20 mg
Placebo capsule for IPX056 20 mg
Drug: Placebo IPX056 40 mg
Placebo capsule for IPX056 40 mg
Placebo - OLE
A single dose of Placebo Baclofen Tablet, Placebo IPX056 20 mg and Placebo IPX056 40 mg (Part 1), 9 week Open label extension of IPX056 (flexible dose design,IPX056 10 mg, IPX056 20 mg, IPX056 30 mg, IPX056 35 mg, or IPX056 40 mg)
Drug: IPX056 20 mg
IPX056 Extended Release capsule containing 20 mg baclofen
Other Name: Baclofen ER 20 mg
Drug: IPX056 40 mg
IPX056 Extended Release capsule containing 40 mg baclofen
Other Name: Baclofen ER 40 mg
Drug: Encapsulated Baclofen 20 mg
Baclofen 20mg tablet was encapsulated for blinding.
Other Name: Active comparator
Drug: Placebo Baclofen Tablet
Placebo capsule encapsulated placebo Baclofen tablet
Drug: IPX056 10 mg
IPX056 Extended Release capsule containing 10 mg baclofen
Other Name: Baclofen ER 10 mg
Drug: IPX056 30 mg
IPX056 Extended Release capsule containing 30 mg baclofen
Other Name: Baclofen ER 30 mg
Drug: IPX056 35 mg
IPX056 Extended Release capsule containing 35 mg baclofen
Other Name: Baclofen ER 35 mg
Drug: Placebo IPX056 20 mg
Placebo capsule for IPX056 20 mg
Drug: Placebo IPX056 40 mg
Placebo capsule for IPX056 40 mg

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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00488839


  Hide Study Locations
Locations
United States, Arizona
Northwest NeuroSpecialists
Tucson, Arizona, United States, 85741
United States, Arkansas
OrthoArkansas, P. A.
Little Rock, Arkansas, United States, 72201
OrthoArkansas, P.A.
Little Rock, Arkansas, United States, 72201
United States, Colorado
Patricia Fodor
Colorado Springs, Colorado, United States, 80919
United States, Florida
Sunrise Clinical Research
Hollywood, Florida, United States, 33021
Meridien Research
Tampa, Florida, United States, 33606
United States, Georgia
MS Center of Atlanta
Atlanta, Georgia, United States, 30327
United States, Illinois
OSF Saint Francis Medical Center
Peoria, Illinois, United States, 61637
United States, Indiana
Elkhardt Clinic
Elkhart, Indiana, United States, 46514
United States, Kansas
MidAmerica Neuroscience Institute
Lenexa, Kansas, United States, 66214
United States, Massachusetts
Springfield Neurology
Springfield, Massachusetts, United States, 01104
United States, Michigan
General Clinical Research Center 7A
Ann Arbor, Michigan, United States, 48109
Medex Healthcare Research, Inc.
St. Louis, Michigan, United States, 63117
Northern Michigan Neurology
Traverse City, Michigan, United States, 49684
United States, New York
Winthrop University Hospital
Mineola, New York, United States, 11501
United States, Pennsylvania
Crozer Chester Medical Center
Upland, Pennsylvania, United States, 19013
United States, Texas
Bhupesh Dihenia
Lubbock, Texas, United States, 79410
Integra Clinical Research
San Antonio, Texas, United States, 78229
United States, Vermont
Neurological Research Center
Bennington, Vermont, United States, 05201
United States, Virginia
Virginia Commonwealth University Medical Center
Richmond, Virginia, United States, 23298
Canada, Quebec
Montreal Neurological Institute and Hospital
Montreal, Quebec, Canada, H3A 2B4
Canada
Foothills Medical Centre, MS Clinic, SSB
Calgary, Canada, t2n 2t9
Estonia
West-Tallinn Central Hospital
Tallinn, Estonia, 10617
Latvia
Vecmilgravis Hospital, Latvian Maritime Medicine Center
Riga, Latvia
Ukraine
Chernihiv Regional Hospital Department of Neurology
Chernihiv, Ukraine, 14029
Neurology and Neurosurgery Dpt., Postgraduation training faculty, Dnipropetrovsk State medical Academy
Dnipropetrovsk, Ukraine, 49027
Institue of Neruology, Psychiatry and Narcology of AMS of Ukraine
Kharkiv, Ukraine, 61068
Department of nervous system demyelization diseases of City Clinical Hospital
Kyiv, Ukraine, 03110
Odessa Regional Clinical Hospital
Odessa, Ukraine, 65025
Neurology department of Ukraine medical stomatological akademy
Poltava, Ukraine, 36024
Vinnytsya Regional Psychoneurological Hospital
Vinnytsya, Ukraine, 21005
Sponsors and Collaborators
IMPAX Laboratories, Inc.
Investigators
Study Director: Ann Hsu, PhD IMPAX Laboratories, Inc.
  More Information

Responsible Party: IMPAX Laboratories, Inc.
ClinicalTrials.gov Identifier: NCT00488839     History of Changes
Other Study ID Numbers: IPX056-B06-03
2007-000236-16 ( EudraCT Number )
First Submitted: June 18, 2007
First Posted: June 20, 2007
Last Update Posted: February 13, 2017
Last Verified: February 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by IMPAX Laboratories, Inc.:
Spasticity
Multiple Sclerosis

Additional relevant MeSH terms:
Sclerosis
Multiple Sclerosis
Muscle Spasticity
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Muscular Diseases
Musculoskeletal Diseases
Muscle Hypertonia
Neuromuscular Manifestations
Neurologic Manifestations
Signs and Symptoms
Baclofen
Muscle Relaxants, Central
Physiological Effects of Drugs
Neuromuscular Agents
Peripheral Nervous System Agents
GABA-B Receptor Agonists
GABA Agonists
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action