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Efficacy, Safety and Pharmacokinetics of Topical Timolol in Infants With Infantile Hemangioma (IH) (TIM01)

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: NCT02913612
Recruitment Status : Completed
First Posted : September 26, 2016
Last Update Posted : May 14, 2020
Sponsor:
Collaborators:
The Emmes Company, LLC
National Institutes of Health (NIH)
Information provided by (Responsible Party):
Kanecia Zimmerman, MD MPH, Duke University

Brief Summary:
The purpose of this study is to assess the safety and efficacy of Timolol 0.25% and 0.5% doses.

Condition or disease Intervention/treatment Phase
Infantile Hemangioma Drug: 0.25% Timolol Maleate Gel Forming Solution Drug: 0.5% Timolol Maleate Gel Forming Solution Phase 2

Detailed Description:
Primary: Describe the efficacy of 0.25% and 0.5% topical timolol maleate GFS as assessed through IH changes in volume. Secondary: Describe the safety and PK of topical timolol maleate GFS for treatment of IH.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 105 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Efficacy, Safety, and Pharmacokinetics of Timolol in Infants With Infantile Hemangioma (IH)
Actual Study Start Date : May 5, 2017
Actual Primary Completion Date : January 28, 2020
Actual Study Completion Date : April 28, 2020

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MedlinePlus related topics: Birthmarks

Arm Intervention/treatment
Experimental: Intervention Group
Subjects assigned to this arm will be randomized to either 0.25% Timolol or 0.5% Timolol for 180 days. If during the 180 days the subject is considered a treatment failure, the subject will be unblinded. If the subject is on 0.25% timolol they will be changed to 0.5% timolol, if on 0.5% timolol the treating physician will decide to either continue 0.5% timolol or withdraw the subject and begin alternative treatment.
Drug: 0.25% Timolol Maleate Gel Forming Solution
50:50 Randomized 0.25% Timolol Maleate Gel Forming Solution

Drug: 0.5% Timolol Maleate Gel Forming Solution
50:50 Randomized 0.5% Timolol Maleate Gel Forming Solution

No Intervention: Non-Intervention Group
Subjects assigned to this group will not receive treatment. The subject will only be photographed on the same schedule as the intervention group.



Primary Outcome Measures :
  1. Comparison of partial response of hemangioma volume within the treat arm compared to the untreated controls [ Time Frame: 180 days ]
    Partial response of hemangioma volume from baseline to 180 days within each treatment arm and compared with untreated controls


Secondary Outcome Measures :
  1. Efficacy Comparison of proportion of infants with partial response or greater change in volume [ Time Frame: 180 days ]
    Percentage of participants with partial response of change in volume from baseline to 180 days within each treatment arm compared with the untreated controls.

  2. Efficacy comparison of proportion of infants with partial response between the two treatment arms [ Time Frame: 180 days ]
    Percentage of participants with partial response of change in color from baseline to 180 days between the two treatment arms and compared with untreated controls

  3. Efficacy comparison of partial response of infants with partial response of hemangioma color between the treatment arms [ Time Frame: 180 days ]
    Percentage of participants with partial response of change in color from baseline to 180 days between the two arms.

  4. Change in Efficacy Improvement of hemangioma complication within the treatment arms [ Time Frame: Baseline and Day 180 ]
    Change in the dynamic complication scale results within each treatment arm

  5. Efficacy assessment of time to partial response in both treatment arms [ Time Frame: 180 days ]
    Assess time to partial response by comparing baseline to day 30, day 60, day 120 and 120 in both treatment arms

  6. Change in Efficacy assessment of Quality of Life assessment for infants in both treatment arms [ Time Frame: Baseline and Day 180 ]
    Absolute change in the Quality of Life score within each treatment arm

  7. Rate of Serious Adverse Events and Adverse Events of special interest in treated infants in both arms [ Time Frame: 270 days ]
    Rate of serious adverse events and adverse events of special interest for infants in both treatment arms

  8. Pharmacokinetics (PK) Analysis measuring clearance of Timolol in Plasma specimen [ Time Frame: Up to 12 hours ]
    The PK blood samples will be 1.0 ml each and collected between the following timeframes after application of Timolol: within 2 hours, 2-4 hours, 5-7 hours, 8-10 hours or 11-12 hours.

  9. Pharmacokinetics (PK) Analysis measuring Volume of Distribution of Timolol in plasma specimen [ Time Frame: Up to 12 hours ]
    The PK blood samples will be 1.0 ml each and collected between the following timeframes after application of Timolol: within 2 hours, 2-4 hours, 5-7 hours, 8-10 hours or 11-12 hours.

  10. Pharmacokinetics (PK) Analysis measuring area under the curve of Timolol in plasma specimen [ Time Frame: Up to 12 hours ]
    The PK blood samples will be 1.0 ml each and collected between the following timeframes after application of Timolol: within 2 hours, 2-4 hours, 5-7 hours, 8-10 hours or 11-12 hours.

  11. Pharmacokinetics (PK) Analysis measuring maximum concentration of Timolol in plasma specimen [ Time Frame: Up to 12 hours ]
    The PK blood samples will be 1.0 ml each and collected between the following timeframes after application of Timolol: within 2 hours, 2-4 hours, 5-7 hours, 8-10 hours or 11-12 hours.



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Ages Eligible for Study:   up to 84 Days   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  1. Documented informed consent from legal guardian
  2. 0-84 days postnatal age at time of first study dose or when enrolled into the non-intervention cohort.
  3. Clinical diagnosis of superficial cutaneous or mucosal infantile hemangioma (must include all of the following):

    1. Superficial lesion in the dermis
    2. Thin <2 mm in thickness
    3. Small >=5 cm at its longest dimension and <=10cm2
    4. Involves skin or keratinized mucosa

Exclusion Criteria

  1. History of previous treatment with any pharmacologic or laser therapy for IH
  2. Ongoing therapy with an oral beta blocker or oral corticosteroid (e.g., cardiac arrhythmia, adrenal insufficiency, upper airway obstruction, tetralogy of fallot (TOF), hypertension, reactive airways disease)
  3. IH that requires systemic therapy (defined by dynamic complication scale >3)
  4. IH of the non-keratinized mucosa
  5. Infants with more than one hemangioma that requires therapy
  6. Hemodynamically significant cardiovascular disease, as determined by the investigator
  7. Known allergy to beta blockers or vehicle
  8. Heart rate <100 beats per minute at screening visit
  9. Known prenatal or postnatal diagnosis of 2nd/3rd degree atrioventricular block
  10. History of Reactive Airways Disease (RAD)
  11. Any condition which would make the participant, in the opinion of the investigator unsuitable for the study.

Information from the National Library of Medicine

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): NCT02913612


Locations
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United States, Illinois
Ann and Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, United States, 60611
United States, Indiana
Indiana University Health
Indianapolis, Indiana, United States, 46202
United States, Maryland
Johns Hopkins Medical Center
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Boston Children's Hospital
Boston, Massachusetts, United States, 02115
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, New Hampshire
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
United States, Pennsylvania
Children's Hospital of Philadephia
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
The University of Texas Medical School at Houston
Houston, Texas, United States, 77030
DCOL Center for Clinical Research
Longview, Texas, United States, 75605
United States, Wisconsin
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Kanecia Zimmerman, MD MPH
The Emmes Company, LLC
National Institutes of Health (NIH)
Investigators
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Principal Investigator: Kanecia Zimmerman, MD, MHS Duke Clinical Research Institute
Study Chair: Kristin Holland, MD Medical College of Wisconsin

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Responsible Party: Kanecia Zimmerman, MD MPH, Principal Investigator, Duke University
ClinicalTrials.gov Identifier: NCT02913612    
Other Study ID Numbers: Pro00068212
First Posted: September 26, 2016    Key Record Dates
Last Update Posted: May 14, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Kanecia Zimmerman, MD MPH, Duke University:
Hemangioma
Infantile Hemangioma
Pharmacokinetics
Additional relevant MeSH terms:
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Hemangioma
Hemangioma, Capillary
Port-Wine Stain
Neoplasms, Vascular Tissue
Neoplasms by Histologic Type
Neoplasms
Skin Abnormalities
Congenital Abnormalities
Skin Diseases
Timolol
Pharmaceutical Solutions
Maleic acid
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Antihypertensive Agents
Enzyme Inhibitors