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

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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

Tracking Information
First Submitted Date  ICMJE August 12, 2016
First Posted Date  ICMJE September 26, 2016
Last Update Posted Date May 14, 2020
Actual Study Start Date  ICMJE May 5, 2017
Actual Primary Completion Date January 28, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 30, 2018)
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
Original Primary Outcome Measures  ICMJE
 (submitted: September 21, 2016)
Comparison of partial response of hemangioma color within the treat arm compared to the untreated controls [ Time Frame: 180 days ]
Partial response of hemangioma color from baseline to 180 days within each treatment arm and compared with untreated controls
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 5, 2019)
  • 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.
  • 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
  • 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.
  • 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
  • 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
  • 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
  • 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
  • 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.
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 21, 2016)
  • 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.
  • 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
  • Efficacy comparison of partial response of infants with partial response of hemangioma volume between the treatment arms [ Time Frame: 180 days ]
    Percentage of participants with partial response of change in volume from baseline to 180 days between the two arms.
  • 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
  • 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
  • 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
  • Rate of Serious Adverse Events and Adverse Events of special interest in treated infants in both arms [ Time Frame: 180 days ]
    Rate of serious adverse events and adverse events of special interest for infants in both treatment arms
  • 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.
  • 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.
  • 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.
  • 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy, Safety and Pharmacokinetics of Topical Timolol in Infants With Infantile Hemangioma (IH)
Official Title  ICMJE Efficacy, Safety, and Pharmacokinetics of Timolol in Infants With Infantile Hemangioma (IH)
Brief Summary The purpose of this study is to assess the safety and efficacy of Timolol 0.25% and 0.5% doses.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Infantile Hemangioma
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: 0.25% Timolol Maleate Gel Forming Solution
    • Drug: 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.
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 13, 2020)
105
Original Estimated Enrollment  ICMJE
 (submitted: September 21, 2016)
110
Actual Study Completion Date  ICMJE April 28, 2020
Actual Primary Completion Date January 28, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 84 Days   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02913612
Other Study ID Numbers  ICMJE Pro00068212
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Kanecia Zimmerman, MD MPH, Duke University
Study Sponsor  ICMJE Kanecia Zimmerman, MD MPH
Collaborators  ICMJE
  • The Emmes Company, LLC
  • National Institutes of Health (NIH)
Investigators  ICMJE
Principal Investigator: Kanecia Zimmerman, MD, MHS Duke Clinical Research Institute
Study Chair: Kristin Holland, MD Medical College of Wisconsin
PRS Account Duke University
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP