IPX056 in Subjects With Established Spasticity Resulting From Multiple Sclerosis

October 25, 2019 updated by: Impax Laboratories, LLC

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

173

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: 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 Names:
  • Baclofen ER 20 mg
Drug: IPX056 40 mg
IPX056 Extended Release capsule containing 40 mg baclofen
Other Names:
  • Baclofen ER 40 mg
Drug: Encapsulated Baclofen 20 mg
Baclofen 20mg tablet was encapsulated for blinding.
Other Names:
  • 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 Names:
  • Baclofen ER 10 mg
Drug: IPX056 30 mg
IPX056 Extended Release capsule containing 30 mg baclofen
Other Names:
  • Baclofen ER 30 mg
Drug: IPX056 35 mg
IPX056 Extended Release capsule containing 35 mg baclofen
Other Names:
  • Baclofen ER 35 mg
Drug: Placebo IPX056 40 mg
Placebo capsule for IPX056 40 mg
Other: 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 Names:
  • Baclofen ER 20 mg
Drug: IPX056 40 mg
IPX056 Extended Release capsule containing 40 mg baclofen
Other Names:
  • Baclofen ER 40 mg
Drug: Encapsulated Baclofen 20 mg
Baclofen 20mg tablet was encapsulated for blinding.
Other Names:
  • 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 Names:
  • Baclofen ER 10 mg
Drug: IPX056 30 mg
IPX056 Extended Release capsule containing 30 mg baclofen
Other Names:
  • Baclofen ER 30 mg
Drug: IPX056 35 mg
IPX056 Extended Release capsule containing 35 mg baclofen
Other Names:
  • Baclofen ER 35 mg
Drug: Placebo IPX056 20 mg
Placebo capsule for IPX056 20 mg
Other: 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 Names:
  • Baclofen ER 20 mg
Drug: IPX056 40 mg
IPX056 Extended Release capsule containing 40 mg baclofen
Other Names:
  • Baclofen ER 40 mg
Drug: Encapsulated Baclofen 20 mg
Baclofen 20mg tablet was encapsulated for blinding.
Other Names:
  • Active comparator
Drug: IPX056 10 mg
IPX056 Extended Release capsule containing 10 mg baclofen
Other Names:
  • Baclofen ER 10 mg
Drug: IPX056 30 mg
IPX056 Extended Release capsule containing 30 mg baclofen
Other Names:
  • Baclofen ER 30 mg
Drug: IPX056 35 mg
IPX056 Extended Release capsule containing 35 mg baclofen
Other Names:
  • Baclofen ER 35 mg
Drug: Placebo IPX056 40 mg
Placebo capsule for IPX056 40 mg
Drug: Placebo IPX056 20 mg
Placebo capsule for IPX056 20 mg
Other: 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 Names:
  • Baclofen ER 20 mg
Drug: IPX056 40 mg
IPX056 Extended Release capsule containing 40 mg baclofen
Other Names:
  • Baclofen ER 40 mg
Drug: Encapsulated Baclofen 20 mg
Baclofen 20mg tablet was encapsulated for blinding.
Other Names:
  • 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 Names:
  • Baclofen ER 10 mg
Drug: IPX056 30 mg
IPX056 Extended Release capsule containing 30 mg baclofen
Other Names:
  • Baclofen ER 30 mg
Drug: IPX056 35 mg
IPX056 Extended Release capsule containing 35 mg baclofen
Other Names:
  • Baclofen ER 35 mg
Drug: Placebo IPX056 40 mg
Placebo capsule for IPX056 40 mg
Drug: Placebo IPX056 20 mg
Placebo capsule for IPX056 20 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
12 hours

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Impax Laboratories, LLC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2007

Primary Completion (Actual)

May 1, 2008

Study Completion (Actual)

May 1, 2008

Study Registration Dates

First Submitted

June 18, 2007

First Submitted That Met QC Criteria

June 19, 2007

First Posted (Estimate)

June 20, 2007

Study Record Updates

Last Update Posted (Actual)

November 6, 2019

Last Update Submitted That Met QC Criteria

October 25, 2019

Last Verified

February 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IPX056-B06-03
  • 2007-000236-16 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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