The effect and long-term safety of MK-0887A in children with asthma

• Register: EUCTR
• Last refreshed on: 5 March 2018
• Main ID: EUCTR2009-010110-30-LV
• Date of registration: 29/02/2016
• Prospective Registration: Yes
• Primary sponsor: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
• Public title: The effect and long-term safety of MK-0887A in children with asthma
• Scientific title: A phase III, randomized, active-controlled, parallel-group clinical trial to study the efficacy and long-term safety of mometasone furoate / formoterol fumarate (MF/F, MK-0887A [SCH418131]), compared with mometasone furoate (MF, MK-0887 [SCH032088]), in children with persistent asthma - MK-0887A efficacy and long-term safety in children with persistent asthma
• Date of first enrolment: 15/03/2016
• Target sample size: 160
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-010110-30
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Colombia, Denmark, Guatemala, Hungary, Latvia, Mexico, Peru, Romania, Russian Federation, South Africa, United States

Contacts

• Name: Global clinical Trial operation
• Affiliation: Merck Sharp & Dohme Corp., a subsidiary of Merck

• Name: Global clinical Trial operation
• Affiliation: Merck Sharp & Dohme Corp., a subsidiary of Merck

Key inclusion & exclusion criteria

Inclusion criteria:
1.Be willing to give written informed consent/assent (subjects ages 7 to 11 years, would provide an assent, or provide consent in accordance with local regulations) prior to Screening; and the subject’s legal representative must also give written informed consent for the subject to participate in the trial. The subject’s legal representative may also provide written informed consent and the subject provide assent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research.
For the PK Sub-trial: subject and the subject’s legal representative must be willing to actively participate in the main trial and indicate understanding and willingness to participate in the sub-trial by signing the sub-trial specific informed consent/assent.
2.Be between 5 and 11 years of age (inclusive) at Visit 1, of either sex, and of any race.
3.Have a diagnosis of asthma according to the international guidelines of at least 6 months prior to Visit 1 (Global Initiative for Asthma [GINA] Guidelines Available from: http://www.ginasthma.org/).
4.Have asthma that is adequately controlled on a stable dose of ICS/LABA combination therapy for at least 4 weeks prior to Visit 1 according to the clinical judgment of the investigator.
5.Demonstrate at Visit 1, an FEV1 >60% and =90% predicted when all restricted medications have been withheld for the appropriate intervals.
6.Demonstrate at Visit 1, an increase in absolute FEV1 of at least 12% within 30 minutes after administration of albuterol/salbutamol (must be demonstrated according to the procedure specifically defined in Appendix 12.8). If the 12% reversibility criterion is not met at Visit 1, reversibility must be demonstrated prior to the randomization visit (Visit 3).
7.Demonstrate an ability to follow trial procedures (including use of MDI training inhaler, use of open-label run-in medication, use of PEF meter, and use of eDiary [IVRS/IWRS]) to the satisfaction of the investigator/qualified designee prior to randomization.
8.Have clinical laboratory tests (complete blood count [CBC], blood chemistries, including urine pregnancy for female subjects of child-bearing potential [i.e., who have started menstruating], and urinalysis) conducted at Visit 1 documented to be clinically acceptable to the investigator before beginning the Run-in Period. A female subject of childbearing potential (i.e., who has started menstruating) must have a negative urine pregnancy test at Visit 1 to be considered eligible for the trial.
9. Demonstrate the ability to: use an MDI (without spacer) correctly according to protocol-defined procedures at Visit 1 (Screening Visit) and Visit 2 (Run-in Visit); use a peak flow meter correctly and perform spirometry correctly before Visit 2 (Run-in Visit).
10. Be willing (with consent of their parent(s)/guardian [i.e., caregiver]) to discontinue his/her prescribed asthma medication before beginning the Run-in Period, if based upon the medical judgment of the investigator, there is no inherent harm in changing the subject’s current asthma therapy.
Are the trial subjects under 18? yes
Number of subjects for this age range: 160
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1.Requires the use of >8 inhalations per day of albuterol, 100 mcg per actuation (or its equivalent), and/or >2 nebulized treatments per day of 2.5 mg albuterol (or its equivalent), on any 2 consecutive days between the Screening Visit (Visit 1) and the Randomization Visit (Visit 3). If a subject uses both MDI and nebulized formulations of SABA in the same day, then one nebulized treatment is considered equivalent to 4 inhalations of the MDI in order to calculate if the subject has exceeded the equivalent of 8 inhalations in total SABA use for that day.
2.Experiences a clinical worsening of asthma between the Screening Visit (Visit 1) and the Randomization Visit (Visit 3), that results in emergency room visit (for an asthma exacerbation), hospitalization due to asthma, or treatment with additional, excluded asthma medication (other than SABA).
3.Has experienced an upper or lower respiratory tract infection within the 4 weeks prior to Visit 1. If there is evidence of an upper or lower respiratory tract infection at Visit 1 or at Visit 2 (prior to the subject entering the Run-in Period), the subject may be treated as appropriate, and Visit 1 or Visit 2 can be rescheduled to be at least 4 weeks after resolution.
4.Demonstrates <80% compliance with use of trial medication during the 2 week Run-in Period. Compliance will be determined prior to randomization at Visit 3.
5.Is considered to have unstable asthma at the end-of the Run-in Period, based on the clinical judgment of the investigator.
6.Has had greater than 4 asthma exacerbations (defined as a worsening of asthma requiring systemic corticosteroid use and/or a 24-hour or longer stay in an emergency department, urgent care center, and/or hospital) within the 52 weeks prior to Visit 1.
7.Has been taking any restricted medications prior to the Screening Visit (Visit 1) without meeting the required washout timeframes.
8.Has a known or suspected hypersensitivity to ICS, beta2 agonists, or any components of the trial medications.
9. Has had a history of life-threatening asthma, including an asthma episode that required intubation and/or was associated with hypercapnia requiring non-invasive ventilatory support.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Asthma
MedDRA version: 18.1 Level: PT Classification code 10003553 Term: Asthma System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Intervention(s)

Product Name: Mometasone Furoate / Formoterol Fumarate MDI
Product Code: MK-0887A, SCH418131
Pharmaceutical Form: Pressurised inhalation, suspension
INN or Proposed INN: Mometasone Furoate
CAS Number: 83919-23-7
Current Sponsor code: MK-0887
Other descriptive name: SCH032088
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 50-
INN or Proposed INN: Formoterol Fumarate dihydrate
CAS Number: 43229-80-7
Other descriptive name: Formoterol Fumarate
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 5-

Product Name: Mometasone Furoate MDI
Product Code: MK-0887
Pharmaceutical Form: Pressurised inhalation, suspension
INN or Proposed INN: Mometasone Furoate
CAS Number: 83919-23-7
Current Sponsor code: MK-0887
Other descriptive name: SCH032088
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 50-

Primary Outcome(s)

Primary end point(s): The primary efficacy endpoint is the AM post-dose %-predicted FEV1 (measured as the change from AM pre-dose %-predicted FEV1). The AM post-dose %-predicted FEV1 is calculated as the area under the curve from zero to 60 minutes (using the trapezoid rule) after a witnessed dose and divided by the time interval (to preserve the unit, % predicted). This method of calculation provides an aggregate bronchodilatory effect during 1 hour post-dose. A separate AM post-dose %-predicted FEV1 measurement is calculated for each visit, and is evaluated as a change from baseline of the mean across Day 1, Week 1, Week 4, Week 8 and Week 12.

Main Objective: Primary Efficacy Objective:
To demonstrate the efficacy of MF/F 100/10 mcg twice daily, compared with MF 100 mcg twice daily, by evaluating lung function during the first 12 weeks of double-blind treatment in children ages 5–11 years with persistent asthma.

Primary Safety Objective:
To characterize the safety and tolerability of MF/F 100/10 mcg twice daily and MF 100 mcg twice daily based on adverse events reported in association with up to 24 weeks of treatment in children ages 5 to 11 years with persistent asthma.

Secondary Objective: To determine the onset of action for the efficacy of MF/F 100/10 mcg twice daily, compared
with MF 100 mcg twice daily by evaluating % predicted FEV1 am of Day 1 of dosing analyzed beginning at 4h-postdose, 2h, 60, 30, 15 and 5 minutes post-dose and measured as the change from baseline (AM-predose-Day1).
1.To demonstrate the efficacy of MF/F 100/10 mcg twice daily, compared with MF 100 mcg twice daily, on the change from baseline in AM post-dose %-predicted FEV1 as measured during 4 hours post-dose, at Day 1 and Week 12; on the change from baseline in AM pre-dose % predicted FEV1, averaged over weeks 4, 8, and 12 of treatment; on the change from baseline in total daily short-acting ß agonist use across the first 12-weeks of double-blind treatment.
2.To characterize the plasma PK profile of MF and determine PK parameters at steady state after multiple oral inhalations via MDI device in children ages 5-11 years old with persistent asthma.

Timepoint(s) of evaluation of this end point: Day 1, Week 1, Week 4, Week 8 and Week 12

Secondary Outcome(s)

Secondary end point(s): The key secondary endpoint of AM %-predicted FEV1 at each of the 5-, 15-, 30-, and 60-minute, 2- and 4 hour post-dose evaluations on Day 1 of dosing will assess the onset of action of MF/F. Formoterol is characterized by a rapid bronchodilator effect, which may be observed within 5 minutes of administration.

Timepoint(s) of evaluation of this end point: Day 1 of dosing

Secondary ID(s)

MK-0887A-087

P04224

Source(s) of Monetary Support

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.