IPX056 in Subjects With Established Spasticity Resulting From Multiple Sclerosis

Condition(s) targeted: Multiple Sclerosis

Intervention: IPX056 (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: IMPAX Laboratories, Inc.

Official(s) and/or principal investigator(s):
Ann Hsu, PhD, Study Director, Affiliation: IMPAX Laboratories, Inc.

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.

Official title: A Double-Blind, Randomized, Placebo- and Active Comparator- Controlled, Parallel Group, Multinational Study to Evaluate the Pharmacokinetics and Pharmacodynamics of IPX056 in Subjects With Established Spasticity Resulting From Multiple Sclerosis

Study design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: 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

Secondary outcome:

Duration of effect (improvement in Ashworth Scale) for IPX056

Establishment of relationships between baclofen plasma concentration with improvement in Ashworth Scale

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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, dentrolene, 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.

Northwest NeuroSpecialists, Tucson, Arizona 85741, United States; Recruiting
Joan Laguna, Phone: 520-742-1833
Jeanette Wendt, M.D., Principal Investigator

Elkhardt Clinic, Elkhart, Indiana 46514, United States; Recruiting
Randall Gibson, Phone: 574-296-3900
Thomas Vidic, M.D., Principal Investigator

MidAmerica Neuroscience Institute, Lenexa, Kansas 66214, United States; Recruiting
Leigh Kreshel, Phone: 913-894-1500, Ext: 155
Vernon Rowe, M.D., Principal Investigator

Springfield Neurology, Springfield, Massachusetts 01104, United States; Recruiting
Rachel Gutzmer, Phone: 413-781-5045
Michael Rossen, M.D., Principal Investigator

Northern Michigan Neurology, Traverse City, Michigan 49684, United States; Recruiting
Cynthia Conquest, Phone: 231-935-0340
Bradley Evans, M.D., Principal Investigator

Upper Valley Neurology Neurosurgery, Lebanon, New Hampshire 03766, United States; Recruiting
Brian Aldrich, Phone: 603-448-3177
Donald Ayres, M.D., Principal Investigator

Innovative Clincal Trials, San Antonio, Texas 78229, United States; Recruiting
Rhonda Williams, Phone: 210-377-2873
James Garrison, M.D., Principal Investigator

Integra Clinical Research, San Antonio, Texas 78229, United States; Recruiting
Brandi Dunn, Phone: 210-568-0261, Ext: 124
Suzanne Gazada, M.D., Principal Investigator

Bhupesh Dihenia, Lubbock, Texas 79410, United States; Recruiting
Amber Hill, Phone: 806-722-3500
Bhupesh Dihenia, M.D., Principal Investigator

Neurological Research Center, Bennington, Vermont 05201, United States; Recruiting
Judy Button, Phone: 802-447-2598, Ext: 119
Keith Edwards, M.D., Principal Investigator

Starting date: June 2007
Ending date: February 2008
Last updated: June 19, 2007