Established Spasticity Resulting from Multiple Sclerosis MedDRA version: 9.1 Level: LLT Classification code 10041416 Term: Spasticity
Conditions
Interventions
Product Code: IPX056-40 mg
Pharmaceutical Form: Capsule*
INN or Proposed INN: BACLOFEN
CAS Number: 1134470
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-
Pharm
Sponsors
IMPAX Laboratories, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. 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. 2. 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. 3. Has a negative urine drug screen at screening visit. If a positive result is observed, subject must have valid prescription for and must be willing to washout the current drug(s). The subjects will not be enrolled into the study if urine drug screen is positive at PK/PD Visit 1. 4. Has Definite multiple sclerosis by Poser or McDonald Criteria. 5. Expanded Disability Status Scale (EDSS) rating between 3.0-8.0 (Appendices B and C), determined at Screening Visit or within 4 weeks prior to Screening Visit. 6. Has no clinically significant ECG abnormalities and has a blood pressure =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. If female, the subject is: a) pregnant; or planning to become pregnant; or b) breastfeeding; or c) 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). 2. History of allergic or severe intolerance to baclofen. 3. Did not respond to previous baclofen treatment in any formulation. 4. Treated with intrathecal baclofen within the previous 6 months prior to the Screening Visit. 5. Has experienced an exacerbation of MS within 3 months prior to the Screening Visit. 6. 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. 7. Serum creatinine level = 1.5 x ULN (upper limit of normal reference range) at the Screening Visit or requires dialysis. 8. Liver enzyme values = 2 x ULN (upper limit of normal reference range) at the Screening Visit. 9. Uncontrolled peptic ulcers, liver disease, diabetes mellitus, severe or clinically significant bladder sphincter hypertonia, hypertension or heart disease. 10. History of seizure or epilepsy, or is currently taking an anti-convulsant for treatment or control of seizure. 11. Concomitant neurologic conditions causing spasticity (e.g. stroke, cerebral palsy, traumatic brain injury) or rigidity (e.g. Parkinson’s disease). 12. 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. 13. Currently taking antipsychotics, CNS depressants or CNS depression producing medications (including alcohol, sedating antihistamines, barbiturates, hypnotics, narcotics, and phenothiazines), monoamine oxidase inhibitors (MAOI, including furazolidone, isocarboxazid, phenelzine, procarbazine, selegiline, and tranylcypromine), and tricyclics. 14. Unable or unwilling to wash out current anti-spasticity medications, including but not limited to baclofen, benzodiazepines (such asclonazepam and diazepam), cannabinoids, clonidine, cyclobenzaprine, dantrolene, gabapentin, glycine, levetiracetam, orphenadrine, phenytoin, progabide, riluzole, steroids, tizanidine and/or tolperisone for Day 1, Visit 1, procedures. However, these medications will be allowed during open label study. 15. Unable or unwilling to participate 12-hour PK/PD procedures during Visit 1. 16. Lower extremities treated with Botulinum Toxin Type A or B within the previous 4 months, or Phenol or therapeutic alcohol nerve block within 12 months prior to the Screening Visit. 17. History of alcohol abuse or use of recreational drugs within 12 months prior to the Screening Visit. 18. Has received an investigational drug or device within 30 days prior to the Screening Visit. 19. Has clinically significant limitation of passive range of motion around any of the joints being assessed in this study. 20. 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to demonstrate that IPX056 reduces spasticity, measured by Ashworth score, in subjects with multiple sclerosis (MS).;Secondary Objective: 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.;Primary end point(s): Primary Pharmacodynamic/ Efficacy Parameter: 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 at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 hours after dosing during Visit 1 will be the primary efficacy parameter. Additional analysis with appropriate time durations will be performed if the duration of effect for the reference baclofen tablet is less than expected (i.e.; 8 hour). Secondary Efficacy Parameter a Duration of effect (improvement in Ashworth Scale) for IPX056 b. Establishment of relationships between baclofen plasma concentration with improvement in Ashworth Scale Exploratory Efficacy Parameters a. Multiple Sclerosis Impact Scale – 29 b. Spasm Frequency and Nighttime Awakening (Due to Spasm) Score c. Spasticity Control Rating d. Morning stiffness score e. Global Assessment of Efficacy and Tolerability score Safety Parameters: Adverse events, laboratory results, ECG, vital signs, and concomitant medication usage will be evaluated over Pa | — |
Countries
Estonia, Latvia
Outcome results
None listed