Clinical trial NCT00488839 (phase 3, status: completed)
Conditions: multiple sclerosis
ICD codes: G35, C81.18
Drugs: ipx056 20 mg, ipx056 40 mg, encapsulated baclofen 20 mg, placebo baclofen tablet, ipx056 10 mg, ipx056 30 mg, ipx056 35 mg, placebo ipx056 20 mg, placebo ipx056 40 mg
SMILES: NCC(CC(O)=O)C1=CC=C(Cl)C=C1, NCC(CC(O)=O)C1=CC=C(Cl)C=C1, CCCC(O)=O, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O, NCC(CC(O)=O)C1=CC=C(Cl)C=C1, NCC(CC(O)=O)C1=CC=C(Cl)C=C1, NCC(CC(O)=O)C1=CC=C(Cl)C=C1, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
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.