Study identifier:IPX229-B16-01
ClinicalTrials.gov identifier:NCT03275922
EudraCT identifier:N/A
CTIS identifier:N/A
A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Crossover Study To Evaluate The Efficacy And Safety Of Zolmitriptan Nasal Spray For The Treatment Of Acute Migraine In Subjects Ages 6 To 11 Years, With An Open-Label Extension
migraine
Phase 3
No
Placebo ZNS, ZNS
All
374
Interventional
6 Years - 11 Years
Allocation: Randomized
Endpoint Classification: -
Intervention Model: Crossover Assignment
Masking: -
Primary Purpose: Treatment
Verified 01 Jun 2021 by AstraZeneca
AstraZeneca
-
To evaluate the efficacy and safety of zolmitriptan nasal spray (ZNS) in the acute treatment of migraine headache in subjects ages 6 to 11 years. Part 1: Approximately 20 weeks (includes screening and double-blind treatment). • Screening will be performed based on the inclusion exclusion criteria specified in the study protocol. • Randomize approximately 288 subjects into the double-blind crossover phase. • Part 2: Approximately 100 subjects who complete the double-blind crossover phase will enter part 2, a 6 month open-label safety extension (OLE). Efficacy will be evaluated in the double-blind part of the trial. Safety will be evaluated in both the double-blind and the OLE.
Location
Location
Salt Lake City, Utah, United States, 84109
Location
Ann Arbor, Michigan, United States, 48104
Location
Charlottesville, Virginia, United States, 22902
Location
Indianapolis, Indiana, United States, 46256
Location
Pittsburgh, Pennsylvania, United States, 15236
Location
Miami, Florida, United States, 33155
Location
Loxahatchee, Florida, United States, 33470
Location
Savannah, Georgia, United States, 31406
Arms | Assigned Interventions |
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Other: Run-in - ZNS - Placebo - OLE After Run-in period, subjects will be randomized to ZNS followed by placebo ZNS. Upon successful completion of Part 1, subjects may enroll into OLE (Part 2). | Drug: Placebo ZNS Placebo Zolmitriptan Nasal Spray Other Name: Placebo Drug: ZNS Zolmitriptan Nasal Spray |
Other: Run-in - Placebo - ZNS - OLE After Run-in period, subjects will be randomized to placebo ZNS followed by ZNS. Upon successful completion of Part 1, subjects may enroll into OLE (Part 2). | Drug: Placebo ZNS Placebo Zolmitriptan Nasal Spray Other Name: Placebo Drug: ZNS Zolmitriptan Nasal Spray |
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations |
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Significant events and approaches for the overall study following participant enrollment, but prior to group assignment |
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Totals for the numbers of patients are higher than the enrollment numbers because the same patients are counted multiple times for each phase of the study. |
Description | |
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Run-in Period | Patients received placebo during the run-in period |
Low dose period 1 | Low dose group of the double-blind, Period 1 |
High Dose Period 1 | High dose group of the double-blind, period 1 |
Low dose period 2 | Low dose group of the double-blind, period 2 |
High dose period 2 | High dose group of the double-blind, period 2 |
2.5 mg dose OLE | Patients receiving 2.5 mg ZNS during the open-label extension (OLE) |
5 mg dose OLE | Patients receiving 5 mg ZNS during the open-label extension (OLE) |
Run-in Period | Low dose period 1 | High Dose Period 1 | Low dose period 2 | High dose period 2 | 2.5 mg dose OLE | 5 mg dose OLE | |
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STARTED | 300 | 35 | 151 | 32 | 135 | 107 | 28 |
COMPLETED | 186 | 32 | 132 | 31 | 125 | 96 | 27 |
NOT COMPLETED | 114 | 3 | 19 | 1 | 10 | 11 | 1 |
Unknown | 20 | 1 | 4 | 0 | 0 | 2 | 0 |
Non-compliance with study drug | 1 | 0 | 2 | 0 | 0 | 0 | 0 |
Lack of Efficacy | 2 | 0 | 0 | 0 | 0 | 1 | 0 |
Run-in Failure | 90 | 0 | 0 | 0 | 0 | 0 | 0 |
No Treated migraine | 1 | 0 | 3 | 1 | 6 | 0 | 0 |
Lost to Follow-up | 0 | 2 | 6 | 0 | 2 | 6 | 1 |
Adverse Event | 0 | 0 | 1 | 0 | 0 | 1 | 0 |
Withdrawal by Subject | 0 | 0 | 3 | 0 | 2 | 1 | 0 |
Description | |
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2.5 mg | 2.5 mg ZNS < 50 kg Weight Group |
5 mg | >= 50 kg Weight Group |
2.5 mg | 5 mg | Total | |
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Number of Participants
[units: Participants] |
110 | 25 | 135 |
Age Continuous
[1] [units: Years] Mean ± Standard Deviation |
9.0 ± 1.57 | 10.2 ± 8.11 | 9.2 ± 1.55 |
Sex: Female, Male [units: participants] |
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Female | 54 | 10 | 64 |
Male | 56 | 15 | 71 |
Race (NIH/OMB) [units: Participants] |
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American Indian or Alaska Native | 0 | 0 | 0 |
Asian | 3 | 0 | 3 |
Native Hawaiian or Other Pacific Islander | 0 | 1 | 1 |
Black or African American | 43 | 9 | 52 |
White | 61 | 14 | 75 |
More than one race | 0 | 0 | 0 |
Unknown or Not Reported | 3 | 1 | 4 |
Ethnicity (NIH/OMB) [units: Participants] |
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Hispanic or Latino | 24 | 10 | 34 |
Not Hispanic or Latino | 86 | 15 | 101 |
Unknown or Not Reported | 0 | 0 | 0 |
Weight
[2] [units: Weight in kg] Mean ± Standard Deviation |
33.62 ± 7.663 | 60.68 ± 10.119 | 38.63 ± 34.90 |
Measure Type | Primary |
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Measure Name | Pain-free status at 2 hours post treatment |
Measure Description | Headache pain intensity is assessed by the subjects immediately prior to treatment and 2 hours post-dose using a 4-point headache pain intensity scale (severe = 3, moderate = 2, mild = 1, or none = 0). |
Time Frame | 2 hours post-dose |
Safety Issue? | No |
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. |
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Number of patients pain free 2 hours post treatment |
Description | |
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High Dose ZNS | After Run-in period, subjects will be randomized to ZNS followed by placebo ZNS. Upon successful completion of Part 1, subjects may enroll into OLE (Part 2). |
Placebo | After Run-in period, subjects will be randomized to placebo ZNS followed by ZNS. Upon successful completion of Part 1, subjects may enroll into OLE (Part 2). |
High Dose ZNS | Placebo | |
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Number of
Participants Analyzed [units:participants] |
133 | 128 |
Number of Number of patients Pain-Free at 2 hours Analyzed | 45 | 30 |
Pain-free status at 2 hours post treatment [units: participants] |
133 | 128 |
Groups [1] | All groups |
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Method [3] | Other [Generalized Estimating Equation (GEE)] |
P-Value [4] | 0.0777 |
Odds Ratio (OR) [5] | 1.507 |
95% Confidence Interval | ( 0.956 to 2.376 ) |
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Groups [1] | All groups |
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Method [3] | Other [Generalized Estimating Equation] |
P-Value [4] | 0.8456 |
Odds Ratio (OR) [5] | 0.953 |
95% Confidence Interval | ( 0.584 to 1.559 ) |
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Measure Type | Secondary |
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Measure Name | Proportion of subjects who achieve pain-free status at 24 hours post-dose |
Measure Description | The headache pain intensity is assessed by the subjects using a 4-point headache pain intensity scale (severe = 3, moderate = 2, mild = 1, or none = 0). |
Time Frame | 24 hours post-dose |
Safety Issue? | No |
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. |
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number of patients pain free at 24 hours post treatment |
Description | |
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High Dose ZNS | After Run-in period, subjects will be randomized to ZNS followed by placebo ZNS. Upon successful completion of Part 1, subjects may enroll into OLE (Part 2). |
Placebo | After Run-in period, subjects will be randomized to placebo ZNS followed by ZNS. Upon successful completion of Part 1, subjects may enroll into OLE (Part 2). |
High Dose ZNS | Placebo | |
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Number of
Participants Analyzed [units:participants] |
131 | 127 |
Number of Patients pain free Analyzed | 131 | 127 |
Proportion of subjects who achieve pain-free status at 24 hours post-dose [units: Patients] |
97 | 90 |
Groups [1] | All groups |
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Method [3] | Other [Generalized Estimating Equation (GEE)] |
P-Value [4] | 0.4664 |
Odds Ratio (OR) [5] | 1.179 |
95% Confidence Interval | ( 0.757 to 1.835 ) |
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Measure Type | Secondary |
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Measure Name | Headache response at 24 hours post-dose |
Measure Description | The subject diary captures the headache severity using a 4-point headache pain intensity scale (severe = 3, moderate = 2, mild = 1, or none = 0). Headache response is defined as a reduction in moderate (2) or severe (3) pain to mild (1) or no (0) pain at 24 hour post-dose. |
Time Frame | 24 hours post-dose |
Safety Issue? | No |
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. |
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Number of patients pain free at 24 hours post treatment |
Description | |
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High Dose ZNS | After Run-in period, subjects will be randomized to ZNS followed by placebo ZNS. Upon successful completion of Part 1, subjects may enroll into OLE (Part 2). |
Placebo | After Run-in period, subjects will be randomized to placebo ZNS followed by ZNS. Upon successful completion of Part 1, subjects may enroll into OLE (Part 2). |
High Dose ZNS | Placebo | |
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Number of
Participants Analyzed [units:participants] |
131 | 127 |
Headache response at 24 hours post-dose [units: Number of patients] |
112 | 109 |
Groups [1] | All groups |
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Method [3] | Other [Generalized Estimating Equation (GEE)] |
P-Value [4] | 0.953 |
Odds Ratio (OR) [5] | 0.953 |
95% Confidence Interval | ( 0.953 to 1.553 ) |
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Measure Type | Secondary |
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Measure Name | Sustained headache response at 24 hours post-dose |
Measure Description | Sustained headache response is defined as a reduction in migraine headache pain intensity from severe or moderate to mild or none at 2 hours which is then maintained (without a return to moderate or severe pain) at 24 hours with no use of rescue medication prior to the 24 hour assessment. |
Time Frame | 24 hours post-dose |
Safety Issue? | No |
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. |
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Number of patients with sustained Headache Response 2-24 hours after treatment |
Description | |
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High Dose ZNS | After Run-in period, subjects will be randomized to ZNS followed by placebo ZNS. Upon successful completion of Part 1, subjects may enroll into OLE (Part 2). |
Placebo | After Run-in period, subjects will be randomized to placebo ZNS followed by ZNS. Upon successful completion of Part 1, subjects may enroll into OLE (Part 2). |
High Dose ZNS | Placebo | |
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Number of
Participants Analyzed [units:participants] |
133 | 128 |
Sustained headache response at 24 hours post-dose [units: Number of patients] |
52.63 | 35.15 |
Groups [1] | All groups |
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Method [3] | Other [Generalized Estimating Equation] |
P-Value [4] | 0.0056 |
Odds Ratio (OR) [5] | 1.844 |
95% Confidence Interval | ( 1.196 to 2.841 ) |
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Time Frame | Test |
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Additional Description | No text entered. |
Description | |
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Placebo Run-in | Placebo Run-in |
Low dose group <50 kg double-blind Period | Patients weighing < 50 Kg given 1mg ZNS during the double-blind period |
High dose group < 50 kg double-blind period | Patients weighing < 50 kg given 2.5 mg ZNS during the double-blind period |
Low Dose group >= 50 kg double-blind Period | Patients weighing >= 50 kg given 2.5 mg ZNS during the double-blind Period |
High Dose group >= 50 Kg double-blind Period | Patients weighing >= 50 KG given 5 mg ZNS during the double-blind period. |
Placebo | After Run-in period, subjects will be randomized to placebo ZNS followed by ZNS. Upon successful completion of Part 1, subjects may enroll into OLE (Part 2). |
OLE 2.5 MG ZNS | Patients receiving 2.5 mg of ZNS during part 2 (The open-label extension) |
OLE 5 mg ZNS | Patients receiving 5 mg of ZNS during part 2 (The open-label extension) |
Placebo Run-in | Low dose group <50 kg double-blind Period | High dose group < 50 kg double-blind period | Low Dose group >= 50 kg double-blind Period | High Dose group >= 50 Kg double-blind Period | Placebo | OLE 2.5 MG ZNS | OLE 5 mg ZNS | |
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Total, serious adverse events | ||||||||
# participants affected / at risk | 0/300 (0.00%) | 0/26 (0.00%) | 0/114 (0.00%) | 0/6 (0.00%) | 0/19 (0.00%) | 0/159 (0.00%) | 0/112 (0.00%) | 0/29 (0.00%) |
Time Frame | Test |
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Additional Description | No text entered. |
Threshold above which other adverse events are reported | 5% |
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Description | |
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Placebo Run-in | Placebo Run-in |
Low dose group <50 kg double-blind Period | Patients weighing < 50 Kg given 1mg ZNS during the double-blind period |
High dose group < 50 kg double-blind period | Patients weighing < 50 kg given 2.5 mg ZNS during the double-blind period |
Low Dose group >= 50 kg double-blind Period | Patients weighing >= 50 kg given 2.5 mg ZNS during the double-blind Period |
High Dose group >= 50 Kg double-blind Period | Patients weighing >= 50 KG given 5 mg ZNS during the double-blind period. |
Placebo | After Run-in period, subjects will be randomized to placebo ZNS followed by ZNS. Upon successful completion of Part 1, subjects may enroll into OLE (Part 2). |
OLE 2.5 MG ZNS | Patients receiving 2.5 mg of ZNS during part 2 (The open-label extension) |
OLE 5 mg ZNS | Patients receiving 5 mg of ZNS during part 2 (The open-label extension) |
Placebo Run-in | Low dose group <50 kg double-blind Period | High dose group < 50 kg double-blind period | Low Dose group >= 50 kg double-blind Period | High Dose group >= 50 Kg double-blind Period | Placebo | OLE 2.5 MG ZNS | OLE 5 mg ZNS | |
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Total, other (not including serious) adverse events | ||||||||
# participants affected / at risk | 0/300 (0.00%) | 0/26 (0.00%) | 0/114 (0.00%) | 0/6 (0.00%) | 0/19 (0.00%) | 0/159 (0.00%) | 0/112 (0.00%) | 0/29 (0.00%) |
Principal Investigators are NOT employed by the organization sponsoring the study. |
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. |
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data |
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Name/Title: | Clinical Study Information Center |
Organization: | AstraZeneca |
Phone | 1-877-240-9479 |
E-mail: | [email protected] |
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