Oral Baclofen Pharmacokinetics and Pharmacodynamics in Children With Spasticity (Best PK/PD)
|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.|
|ClinicalTrials.gov Identifier: NCT00607542|
Recruitment Status : Completed
First Posted : February 5, 2008
Last Update Posted : December 6, 2011
- Study Details
- Tabular View
- Results Submitted
- How to Read a Study Record
|Condition or disease||Intervention/treatment||Phase|
|Spasticity Cerebral Palsy||Drug: baclofen||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||61 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Pediatric Pharmacokinetic and Pharmacodynamic Study of Oral Baclofen for the Treatment of Spasticity Associated With Cerebral Palsy|
|Study Start Date :||November 2008|
|Actual Primary Completion Date :||January 2011|
|Actual Study Completion Date :||January 2011|
Active Comparator: 1
starting dose of baclofen 2.5 mg PO TID with dose escalation as tolerated
2.5 mg oral baclofen tablets given three times a day; dose gradually escalated as specified in the protocol
Other Name: Lioresal
- Determine pharmacokinetic parameters of oral baclofen in children with spasticity associated with cerebral palsy (CP). [ Time Frame: 1 year ]
- Describe the relationship between plasma concentrations of oral baclofen and clinical measures of spasticity. [ Time Frame: 1 year ]
- Determine optimal dosing range and interval for administration of oral baclofen for use in a randomized clinical trial of safety and efficacy. [ Time Frame: 1 year ]
- Describe the relationship between plasma concentrations of oral baclofen and measures of strength, function, ease of care, pain/comfort and health related quality of life. [ Time Frame: 1 year ]
- Describe the safety and tolerability of oral baclofen in children with spasticity associated with CP. [ Time Frame: 1 year ]
- Investigate preliminarily whether oral baclofen improves dystonia [ Time Frame: 1 year ]
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:||2 Years to 16 Years (Child)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Males and females aged 2-16 years, inclusive.
- Triceps skinfold thickness between the 5th and 95th percentiles for age (Refer to Appendix 3).
- Gross Motor Function Classification Scale (GMFCS) Level II - V (GMFCS classifies children by functional mobility with Level I indicating minimal motor disability and V indicating total body involvement and dependence on others for mobility (Palisano et al, 1997).
- Ashworth score of 2 or higher in at least one arm and one leg (knee + elbow flexors and/or extensors).
- Cerebral Palsy: Motor disability due to a static, non-progressive brain injury/ malformation occurring prenatally or any time prior to the age of 2 years.
- No history of baclofen use within the past 4 months.
- Female subject, is premenarchal, or is incapable of pregnancy because of a hysterectomy or tubal ligation; or female subject who is sexually active and capable of pregnancy, has been using an acceptable method of contraception (hormonal contraceptives, intrauterine device, spermicide and barrier) for at least one month prior to study entry and agrees to continue to use one of these for the duration of the study; or female subject who is sexually abstinent and capable of pregnancy, agrees to continued abstinence or to use an acceptable method of birth control (either intrauterine device or spermicide and barrier) should sexual activity commence.
- Subject ≥10 years of age has negative urine tests at screening and baseline for alcohol, non-medically prescribed drugs of abuse, and no history of tobacco use.
- Hypersensitivity to baclofen.
- Selective dorsal rhizotomy.
- Active intrathecal baclofen pump within the past 6 months.
- Use of botulinum toxin in past 4 months or use any time during the study.
- Use of tone altering medications (e.g. baclofen, benzodiazepines, levodopa, trihexyphenidyl) for >3 consecutive days duration within the past 4 months.
- Start of any drug or product known to be a significant cytochrome P450 enzyme inducer or inhibitor within the past 30 days.
- Orthopaedic surgery within the past year or any time during the study.
- Abdominal surgery within the past six months or any time during the study.
- Uncontrolled seizures (baseline seizure frequency >1 per month or history of more than 2 prolonged seizures lasting longer than 5 minutes duration within the past year.
- Severe behavior difficulties or psychiatric disturbance
- Proven gastric dysmotility: known history of abnormal gastric emptying study and/or history of vomiting 3 or more times per week.
- Severe Gastroesophageal Reflux Disease: known history of esophagitis (documented on abnormal endoscopy or biopsy).
- Malnutrition: defined as triceps skin fold thickness less than 5th or greater than 95th percentile for age.
- Renal or Liver disease: Elevated bilirubin, LFTs greater than twice the upper limit of normal, reduced BUN/Cr ratio (<5), or abnormal creatinine clearance that is clinically significant as determined by the investigator.
- Abnormal CBC: Anemia, polycythemia, neutropenia, leukocytosis, thrombocytopenia, or thrombocytosis clinically significant as determined by the investigator.
- Pregnancy or lactation.
- Severe respiratory or cardiac disease: Requirement for prolonged supplemental oxygen (>7 days), history of clinically significant congenital heart disease, congestive heart failure or cardiomegaly, and/or hospital admission within past 6 months for cardiac symptoms or respiratory distress.
- Previous baclofen failure: Lack of response to baclofen or presence of unacceptable side effects. If previous baclofen therapy was tried >4 months prior to study and discontinued, the decision to enroll subject will be at the discretion of the site investigator and reason for discontinuation of oral baclofen will be recorded.
- Use of medications that interfere with measurements of serum creatinine levels within the past 14 days (e.g., trimethoprim-sulfa, fibric acid derivatives other than gemfibrizol, keto acids, salicylates, some cephalosporins, cimetidine, phenacemide) .
- Subject tests positive at screening for the hepatitis B surface antigen or hepatitis C antibody, or has a history of a positive result for one of these tests.
- Subject is known to have tested seropositive for the human immunodeficiency virus (HIV) or subject is concomitantly receiving anti-retroviral therapy.
- Any serious, unstable medical illness or clinically significant abnormal laboratory assessment that would adversely impact the scientific interpretability or unduly increase the risks of the protocol.
- Subject has a disorder or history of a condition, other than that related to CP that could interfere with drug absorption, distribution, metabolism, or excretion.
- Any condition which would make the patient
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): NCT00607542
|United States, Illinois|
|Rehabilitation Institute of Chicago|
|Chicago, Illinois, United States, 60611|
|United States, Louisiana|
|Children's Hospital of Lousiana|
|New Orleans, Louisiana, United States, 70118|
|United States, Maryland|
|Kennedy Krieger Institute|
|Baltimore, Maryland, United States, 21205|
|United States, Minnesota|
|Gillette Children's Speciality Healthcare|
|St. Paul, Minnesota, United States, 55101|
|United States, Missouri|
|Children's Mercy Hospital and Clinics|
|Kansas City, Missouri, United States, 64108|
|Washington Univeristy - St. Louis Children's hospital|
|St. Louis, Missouri, United States, 63110-1093|
|United States, New York|
|SUNY Upstate Medical University|
|Syracuse, New York, United States, 13210|
|United States, Ohio|
|Cincinnati Children's Hospital Medical Center|
|Cincinnati, Ohio, United States, 45229-3039|
|United States, Texas|
|Texas Children's Hospital|
|Houston, Texas, United States, 77030|
|United States, Virginia|
|Kluge Children's Rehabilitation Center - University of Virginia|
|Charlottesville, Virginia, United States, 22903|
|United States, Washington|
|Seattle Children's Hospital|
|Seattle, Washington, United States, 98105|
|Principal Investigator:||Janice Brunstrom, MD||Washington University of St. Louis|
|Principal Investigator:||Richard Stevenson, MD||University of Virginia|
|Responsible Party:||Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)|
|Other Study ID Numbers:||
|First Posted:||February 5, 2008 Key Record Dates|
|Last Update Posted:||December 6, 2011|
|Last Verified:||February 2011|
Nervous System Diseases
Brain Damage, Chronic
Central Nervous System Diseases
Muscle Relaxants, Central
Physiological Effects of Drugs
Peripheral Nervous System Agents
GABA-B Receptor Agonists
Molecular Mechanisms of Pharmacological Action