Oral Baclofen Pharmacokinetics and Pharmacodynamics in Children With Spasticity

NCT ID: NCT00607542

Last Updated: 2011-12-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

61 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-11-30

Study Completion Date

2011-01-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

Oral baclofen is used commonly to treat spasticity in children with cerebral palsy. Although for adults there is dosing,safety and efficacy information in the package insert, this is not the case for children. The purpose of this study is to determine how fast the drug is cleared from the body, the correct dose, and long-term safety and efficacy for children with spasticity.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Although oral baclofen has been used for several decades for the treatment of spasticity in adults and in children, there is very little data regarding the pharmacokinetic (PK) or pharmacodynamic (PD) properties of baclofen in children. Therefore, pediatric guidelines, including dose ranges, dosing schedules, dose escalation strategies and anticipated side effects are extrapolated from adult data and require an assumption that safety and efficacy in children is comparable to that in adults. Furthermore, there is wide variability in dosing strategies among practitioners who treat children with cerebral palsy (CP) with respect to starting doses, maximum doses and rates of dose escalation.Establishment of safe and effective dosing strategies for children with CP requires an understanding of the PK and PD properties of baclofen in children and recognition of individual differences that may contribute to divergent clinical responses to baclofen among children with CP.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Spasticity Cerebral Palsy

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

spasticity cerebral palsy baclofen pharmacokinetics pharmacodynamics dosing safety efficacy

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

1

starting dose of baclofen 2.5 mg PO TID with dose escalation as tolerated

Group Type ACTIVE_COMPARATOR

baclofen

Intervention Type DRUG

2.5 mg oral baclofen tablets given three times a day; dose gradually escalated as specified in the protocol

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

baclofen

2.5 mg oral baclofen tablets given three times a day; dose gradually escalated as specified in the protocol

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Lioresal

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. Males and females aged 2-16 years, inclusive.
2. Triceps skinfold thickness between the 5th and 95th percentiles for age (Refer to Appendix 3).
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).
4. Ashworth score of 2 or higher in at least one arm and one leg (knee + elbow flexors and/or extensors).
5. 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.
6. No history of baclofen use within the past 4 months.
7. 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.
8. 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.

Exclusion Criteria

1. Hypersensitivity to baclofen.
2. Selective dorsal rhizotomy.
3. Active intrathecal baclofen pump within the past 6 months.
4. Use of botulinum toxin in past 4 months or use any time during the study.
5. Use of tone altering medications (e.g. baclofen, benzodiazepines, levodopa, trihexyphenidyl) for \>3 consecutive days duration within the past 4 months.
6. Start of any drug or product known to be a significant cytochrome P450 enzyme inducer or inhibitor within the past 30 days.
7. Orthopaedic surgery within the past year or any time during the study.
8. Abdominal surgery within the past six months or any time during the study.
9. 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.
10. Severe behavior difficulties or psychiatric disturbance
11. Proven gastric dysmotility: known history of abnormal gastric emptying study and/or history of vomiting 3 or more times per week.
12. Severe Gastroesophageal Reflux Disease: known history of esophagitis (documented on abnormal endoscopy or biopsy).
13. Malnutrition: defined as triceps skin fold thickness less than 5th or greater than 95th percentile for age.
14. 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.
15. Abnormal CBC: Anemia, polycythemia, neutropenia, leukocytosis, thrombocytopenia, or thrombocytosis clinically significant as determined by the investigator.
16. Pregnancy or lactation.
17. 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.
18. 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.
19. 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) .
20. 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.
21. Subject is known to have tested seropositive for the human immunodeficiency virus (HIV) or subject is concomitantly receiving anti-retroviral therapy.
22. 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.
23. 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.
24. Any condition which would make the patient
Minimum Eligible Age

2 Years

Maximum Eligible Age

16 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Janice Brunstrom, MD

Role: PRINCIPAL_INVESTIGATOR

Washington University of St. Louis

Richard Stevenson, MD

Role: PRINCIPAL_INVESTIGATOR

University of Virginia

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Rehabilitation Institute of Chicago

Chicago, Illinois, United States

Site Status

Children's Hospital of Lousiana

New Orleans, Louisiana, United States

Site Status

Kennedy Krieger Institute

Baltimore, Maryland, United States

Site Status

Gillette Children's Speciality Healthcare

Saint Paul, Minnesota, United States

Site Status

Children's Mercy Hospital and Clinics

Kansas City, Missouri, United States

Site Status

Washington Univeristy - St. Louis Children's hospital

St Louis, Missouri, United States

Site Status

SUNY Upstate Medical University

Syracuse, New York, United States

Site Status

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

Texas Children's Hospital

Houston, Texas, United States

Site Status

Kluge Children's Rehabilitation Center - University of Virginia

Charlottesville, Virginia, United States

Site Status

Seattle Children's Hospital

Seattle, Washington, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

McLaughlin MJ, He Y, Brunstrom-Hernandez J, Thio LL, Carleton BC, Ross CJD, Gaedigk A, Lewandowski A, Dai H, Jusko WJ, Leeder JS. Pharmacogenomic Variability of Oral Baclofen Clearance and Clinical Response in Children With Cerebral Palsy. PM R. 2018 Mar;10(3):235-243. doi: 10.1016/j.pmrj.2017.08.441. Epub 2017 Sep 1.

Reference Type DERIVED
PMID: 28867665 (View on PubMed)

He Y, Brunstrom-Hernandez JE, Thio LL, Lackey S, Gaebler-Spira D, Kuroda MM, Stashinko E, Hoon AH Jr, Vargus-Adams J, Stevenson RD, Lowenhaupt S, McLaughlin JF, Christensen A, Dosa NP, Butler M, Schwabe A, Lopez C, Roge D, Kennedy D, Tilton A, Krach LE, Lewandowski A, Dai H, Gaedigk A, Leeder JS, Jusko WJ. Population pharmacokinetics of oral baclofen in pediatric patients with cerebral palsy. J Pediatr. 2014 May;164(5):1181-1188.e8. doi: 10.1016/j.jpeds.2014.01.029. Epub 2014 Mar 5.

Reference Type DERIVED
PMID: 24607242 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

267200603421

Identifier Type: -

Identifier Source: secondary_id

NICHD-2005-13-2

Identifier Type: -

Identifier Source: org_study_id