We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

This study is currently recruiting participants.
Verified October 2017 by Chiara Melloni, Duke University Medical Center
Sponsor:
ClinicalTrials.gov Identifier:
NCT02913612
First Posted: September 26, 2016
Last Update Posted: October 3, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
The EMMES Corporation
Information provided by (Responsible Party):
Chiara Melloni, Duke University Medical Center
  Purpose
Multi-center, double-masked randomized, efficacy, safety and pharmacokinetic (PK) study.

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

Study Type: Interventional
Study Design: 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)

Resource links provided by NLM:


Further study details as provided by Chiara Melloni, Duke University Medical Center:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 110
Actual Study Start Date: May 5, 2017
Estimated Study Completion Date: September 28, 2018
Estimated Primary Completion Date: September 28, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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. They subject will only be photographed on the same schedule as the intervention group.

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

Information from the National Library of Medicine

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:   up to 60 Days   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  1. Documented informed consent from legal guardian
  2. 0-60 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): a. Superficial lesion in the dermis b. Thin <2 mm in thickness c. Small <5 cm2 d. 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 for an unrelated condition (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.
  Contacts and Locations
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


Contacts
Contact: Chiara Melloni, MD, MHS 919-668-8646 chiara.melloni@duke.edu
Contact: Beth Drolet, MD 414-955-2818 bdrolet@mcw.edu

Locations
United States, Illinois
Ann and Robert H. Lurie Children's Hospital of Chicago Recruiting
Chicago, Illinois, United States, 60611
Contact: Sarah Chamlin, MD    312-227-6475    schamlin@luriechildrens.org   
Contact: Laura Fearn    312-227-6280    lfearn@luriechildrens.org   
United States, Indiana
Indiana University Health Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Anita Haggstrom, MD    317-944-7744    ahaggstr@iu.edu   
Contact: Flossy Lincoln    317-274-8750    fnjinimb@iupui.edu   
United States, Maryland
Johns Hopkins Medical Center Recruiting
Baltimore, Maryland, United States, 21287
Contact: Kate Puttgen, MD    410-955-5933    kateputtgen@jhmi.edu   
Contact: Hester Lim    410-502-7546    hlim33@jhmi.edu   
United States, Massachusetts
Boston Children's Hospital Not yet recruiting
Boston, Massachusetts, United States, 02115
Contact: Marilyn Liang, MD    617-355-8937    marilyn.liang@childrens.harvard.edu   
Contact: Donia Attia    617-355-4349    donia.attia@childrens.harvard.edu   
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Megha Tollefson, MD    507-284-3579    tollefson.megha@mayo.edu   
Contact: Katrina Pierce    507-266-1078    pierce.katrina@mayo.edu   
United States, New York
Columbia University Medical Center Not yet recruiting
New York, New York, United States, 10032
Contact: Maria Garzon, MD    212-305-5293    mcg2@cumc.columbia.edu   
Contact: Grace Ulerio    212-305-8444    gu2102@cumc.columbia.edu   
United States, Ohio
Cincinnati Children's Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Adrienne Hammill, MD    513-636-3184    adrienne.hammill@cchmc.org   
Contact: Megan Metcalf    513-803-2606    megan.metcalf@cchmc.org   
United States, Pennsylvania
Children's Hospital of Philadephia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Jenna Streicher, MD    215-590-2169    streicherj@email.chop.edu   
United States, Texas
The University of Texas Medical School at Houston Recruiting
Houston, Texas, United States, 77030
Contact: Adelaide Hebert, MD    713-500-8266    adelaide.a.hebert@uth.tmc.edu   
Contact: Maria Lopez    713-500-8266    maria.d.lopez@uth.tmc.edu   
United States, Wisconsin
Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Beth Drolet, MD    414-955-2818    bdrolet@mcw.edu   
Contact: Katherine Mueller    414-955-2846    kamueller@mcw.edu   
Sponsors and Collaborators
Chiara Melloni
The EMMES Corporation
Investigators
Principal Investigator: Chiara Melloni, MD, MHS Duke Clinical Research Institute
Study Chair: Beth Drolet, MD Medical College of Wisconsin
Study Chair: Kristen Holland, MD Medical College of Wisconsin
  More Information

Responsible Party: Chiara Melloni, Principal Investigator, Duke University Medical Center
ClinicalTrials.gov Identifier: NCT02913612     History of Changes
Other Study ID Numbers: Pro00068212
First Submitted: August 12, 2016
First Posted: September 26, 2016
Last Update Posted: October 3, 2017
Last Verified: October 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Chiara Melloni, Duke University Medical Center:
Hemangioma
Infantile Hemangioma
Pharmacokinetics

Additional relevant MeSH terms:
Hemangioma
Hemangioma, Capillary
Port-Wine Stain
Neoplasms, Vascular Tissue
Neoplasms by Histologic Type
Neoplasms
Skin Abnormalities
Congenital Abnormalities
Skin Diseases
Pharmaceutical Solutions
Timolol
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