| Primary | Percentage of Participants With a Worsening in Severity of Gastrointestinal (GI) Adverse Events (AEs) on the GSRS From Day 0 to Day 10 | The GSRS is a weekly recall scale that was modified for daily recall. The 15-question GSRS is summarized with a 7-point Likert scale: no discomfort at all=0; minor discomfort=1; mild discomfort=2; moderate discomfort=3; moderately severe discomfort=4; severe discomfort=5 and very severe discomfort=6. The overall GSRS score is a mean score that ranges from 0 (no symptoms) to 6 (the worst possible symptoms). Worsening in severity was defined as a positive average change from baseline (Day 0) to Day 10 in the GSRS score. Day 0: the day before a participant started randomized treatment (if the GI threshold was reached 1 day previously) or the first day of randomized treatment if the threshold was reached that day. If the threshold was reached >1 day previously, then Day 0 was the last day when the threshold was reached, prior to the first dose. Average change is the sum of changes from baseline in GSRS score over the first 10 days divided by the total of days with a GSRS score. | The MITT: All participants who were randomized, received at least 1 dose of DMF treatment, received at least 1 dose of study treatment (montelukast or placebo) on/after the first DMF dose date, and had at least 1 GSRS score measurement during the Day 1 - Day 10 period. | Posted | | Number | | percentage of participants | | Baseline (Day 0), Day 10 (10 days after Day 0) | | | | ID | Title | Description |
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| OG000 | MITT-Placebo | Participants who reached the predefined threshold in scores on the GSRS during the Run-in Period entered the Study Treatment Period. Participants continued to receive 240 mg DMF twice daily and also received a montelukast-matching placebo tablet once daily by mouth for 8 weeks. Participants received only 240 mg DMF twice daily for 2 weeks after discontinuing treatment with placebo, then were followed for 2 additional weeks before a final phone interview. One participant randomized to placebo was excluded from the MITT. | | OG001 | MITT-Montelukast | Participants who reached the predefined threshold in scores on the GSRS during the Run-in Period entered the Study Treatment Period. Participants continued to receive 240 mg DMF twice daily and also received 10 mg of montelukast once daily by mouth for 8 weeks. Participants received only 240 mg DMF twice daily for 2 weeks after discontinuing treatment with montelukast, then were followed for 2 additional weeks before a final phone interview. |
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| | Group IDs | Group Description | Statistical Method | Statistical Comment | P-Value | P-Value Comment | Parameter Type | Parameter Value | Dispersion Type | Dispersion Value | Confidence Interval Sides | Confidence Interval % | CI Lower Limit | CI Upper Limit | CI Lower Limit Comment | CI Upper Limit Comment | Estimate Comment | Tested Non-Inferiority | Non-Inferiority Type | Non-Inferiority Comment | Other Analysis Description |
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| Odds ratio is the odds of an event in the Montelukast treatment group divided by the odds of an event in the placebo treatment group. P-value is from the likelihood ratio test that the odds ratio is 1. CI = profile likelihood confidence interval. | weighted logistic regression model | | 0.0617 | | Odds Ratio (OR) | 3.931 | | | 2-Sided | 95 | 0.938 | 20.832 | | | | | Superiority | | |
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| Secondary | Average Change From Baseline in GSRS Overall Score at Day 1 to Day 10 | The GSRS is a weekly recall scale that was modified for daily recall. The 15-question GSRS is summarized with a 7-point Likert scale: no discomfort at all=0; minor discomfort=1; mild discomfort=2; moderate discomfort=3; moderately severe discomfort=4; severe discomfort=5 and very severe discomfort=6. The overall GSRS score is a mean score that ranges from 0 (no symptoms) to 6 (the worst possible symptoms). This endpoint reports the average change from baseline (Day 0) at Day 1 to Day 10. Day 0: the day before a participant started randomized treatment (if the GI threshold was reached 1 day previously) or the first day of randomized treatment if the threshold was reached that day. If the threshold was reached >1 day previously, then Day 0 was the last day when the threshold was reached, prior to the first dose. A negative change from baseline indicates that symptoms decreased. | The MITT: All participants who were randomized, received at least 1 dose of DMF treatment, received at least 1 dose of study treatment (montelukast or placebo) on/after the first DMF dose date, and had at least 1 GSRS score measurement during the Day 1 - Day 10 period. | Posted | | Mean | Standard Deviation | units on a scale | | Baseline (Day 0), Day 1 (1 day after Day 0), Day 10 (10 days after Day 0) | | | | ID | Title | Description |
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| OG000 | MITT-Placebo | Participants who reached the predefined threshold in scores on the GSRS during the Run-in Period entered the Study Treatment Period. Participants continued to receive 240 mg DMF twice daily and also received a montelukast-matching placebo tablet once daily by mouth for 8 weeks. Participants received only 240 mg DMF twice daily for 2 weeks after discontinuing treatment with placebo, then were followed for 2 additional weeks before a final phone interview. One participant randomized to placebo was excluded from the MITT. |
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| Secondary | Average Change From Baseline in GSRS Overall Score at Day 1 to Week 10 | The GSRS is a weekly recall scale that was modified for daily recall. The 15-question GSRS is summarized with a 7-point Likert scale: no discomfort at all=0; minor discomfort=1; mild discomfort=2; moderate discomfort=3; moderately severe discomfort=4; severe discomfort=5 and very severe discomfort=6. The overall GSRS score is a mean score that ranges from 0 (no symptoms) to 6 (the worst possible symptoms). This endpoint reports the average change from baseline (Day 0) between Day 1 and Week 10. Day 0: the day before a participant started randomized treatment (if the GI threshold was reached 1 day previously) or the first day of randomized treatment if the threshold was reached that day. If the threshold was reached >1 day previously, then Day 0 was the last day when the threshold was reached, prior to the first dose. A negative change from baseline indicates that symptoms decreased. | The MITT: All participants who were randomized, received at least 1 dose of DMF treatment, received at least 1 dose of study treatment (montelukast or placebo) on/after the first DMF dose date, and had at least 1 GSRS score measurement during the Day 1 - Day 10 period. | Posted | | Mean | Standard Deviation | units on scale | | Baseline (Day 0), Day 1 (1 day after Day 0), Week 10 (10 weeks after Day 0) | | | | ID | Title | Description |
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| OG000 | MITT-Placebo | Participants who reached the predefined threshold in scores on the GSRS during the Run-in Period entered the Study Treatment Period. Participants continued to receive 240 mg DMF twice daily and also received a montelukast-matching placebo tablet once daily by mouth for 8 weeks. Participants received only 240 mg DMF twice daily for 2 weeks after discontinuing treatment with placebo, then were followed for 2 additional weeks before a final phone interview. One participant randomized to placebo was excluded from the MITT. |
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| Secondary | Time to First Worsening From Baseline in GSRS Overall Score at Day 1 to Day 10 | The GSRS is a weekly recall scale that was modified for daily recall. The 15-question GSRS is summarized with a 7-point Likert scale: no discomfort at all=0; minor discomfort=1; mild discomfort=2; moderate discomfort=3; moderately severe discomfort=4; severe discomfort=5 and very severe discomfort=6. The overall GSRS score is a mean score that ranges from 0 (no symptoms) to 6 (the worst possible symptoms). Day 0: the day before a participant started randomized treatment (if the GI threshold was reached 1 day previously) or the first day of randomized treatment if the threshold was reached that day. If the threshold was reached >1 day previously, then Day 0 was the last day when the threshold was reached, prior to the first dose.. Time to the first worsening was defined as the number of days from Day 1 to the first date with a worsened GSRS score. Censoring occurred at Day 10. | The MITT: All participants who were randomized, received at least 1 dose of DMF treatment, received at least 1 dose of study treatment (montelukast or placebo) on/after the first DMF dose date, and had at least 1 GSRS score measurement during the Day 1 - Day 10 period. | Posted | | Median | Inter-Quartile Range | days | | Baseline (Day 0), Day 1 (1 day after Day 0) to Day 10 (10 days after Day 0) | | | | ID | Title | Description |
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| OG000 | MITT-Placebo | Participants who reached the predefined threshold in scores on the GSRS during the Run-in Period entered the Study Treatment Period. Participants continued to receive 240 mg DMF twice daily and also received a montelukast-matching placebo tablet once daily by mouth for 8 weeks. Participants received only 240 mg DMF twice daily for 2 weeks after discontinuing treatment with placebo, then were followed for 2 additional weeks before a final phone interview. One participant randomized to placebo was excluded from the MITT. |
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| Secondary | Time to Recovery to Baseline GSRS Score From Last Occurrence of Worst GSRS Score at Day 1 to Week 8 | The GSRS is a weekly recall scale that was modified for daily recall. The 15-question GSRS is summarized with a 7-point Likert scale: no discomfort at all=0; minor discomfort=1; mild discomfort=2; moderate discomfort=3; moderately severe discomfort=4; severe discomfort=5 and very severe discomfort=6. The overall GSRS score is a mean score that ranges from 0 (no symptoms) to 6 (the worst possible symptoms). Recovery was defined as a GSRS score less than or equal to the Day 0 score. Day 0: the day before a participant started randomized treatment (if the GI threshold was reached 1 day previously) or the first day of randomized treatment if the threshold was reached that day. If the threshold was reached >1 day previously, then Day 0 was the last day when the threshold was reached, prior to the first dose. Time to recovery was defined as the date of recovery minus the date of the last occurrence of the worst score. | The MITT: All participants who were randomized, received at least 1 dose of DMF treatment, received at least 1 dose of study treatment (montelukast or placebo) on/after the first DMF dose date, and had at least 1 GSRS score measurement during the Day 1 - Day 10 period. | Posted | | Median | Inter-Quartile Range | days | | Baseline (Day 0), Day 1 (1 Day after Day 0) to Week 8 (8 weeks after Day 0) | | | | ID | Title | Description |
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| OG000 | MITT-Placebo | Participants who reached the predefined threshold in scores on the GSRS during the Run-in Period entered the Study Treatment Period. Participants continued to receive 240 mg DMF twice daily and also received a montelukast-matching placebo tablet once daily by mouth for 8 weeks. Participants received only 240 mg DMF twice daily for 2 weeks after discontinuing treatment with placebo, then were followed for 2 additional weeks before a final phone interview. One participant randomized to placebo was excluded from the MITT. |
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| Secondary | Average Change From Baseline in GSRS Overall Score at Day 1 to Weeks 1 to 8 | The GSRS is a weekly recall scale that was modified for daily recall. The 15-question GSRS is summarized with a 7-point Likert scale: no discomfort at all=0; minor discomfort=1; mild discomfort=2; moderate discomfort=3; moderately severe discomfort=4; severe discomfort=5 and very severe discomfort=6. The overall GSRS score is a mean score that ranges from 0 (no symptoms) to 6 (the worst possible symptoms). This endpoint reports the average change from baseline (Day 0) between Day 1 and the specified time point. Day 0: the day before a participant started randomized treatment (if the GI threshold was reached 1 day previously) or the first day of randomized treatment if the threshold was reached that day. If the threshold was reached >1 day previously, then Day 0 was the last day when the threshold was reached, prior to the first dose. A negative change from baseline indicates that symptoms decreased. | The MITT: All participants who were randomized, received at least 1 dose of DMF treatment, received at least 1 dose of study treatment (montelukast or placebo) on/after the first DMF dose date, and had at least 1 GSRS score measurement during the Day 1 - Day 10 period. | Posted | | Mean | Standard Deviation | unit on scale | | Baseline (Day 0), Day 1 (1 Day after Day 0), Weeks 1 to 8 (1-8 weeks after Day 0) | | | | ID | Title | Description |
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| OG000 | MITT-Placebo | Participants who reached the predefined threshold in scores on the GSRS during the Run-in Period entered the Study Treatment Period. Participants continued to receive 240 mg DMF twice daily and also received a montelukast-matching placebo tablet once daily by mouth for 8 weeks. Participants received only 240 mg DMF twice daily for 2 weeks after discontinuing treatment with placebo, then were followed for 2 additional weeks before a final phone interview. One participant randomized to placebo was excluded from the MITT. |
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| Secondary | Average Change From Baseline in GSRS Overall Score at Day 0 to 72 Hours From the Initiation of Randomized Study Treatment | The GSRS is a weekly recall scale that was modified for daily recall. The 15-question GSRS is summarized with a 7-point Likert scale: no discomfort at all=0; minor discomfort=1; mild discomfort=2; moderate discomfort=3; moderately severe discomfort=4; severe discomfort=5 and very severe discomfort=6. The overall GSRS score is a mean score that ranges from 0 (no symptoms) to 6 (the worst possible symptoms). This endpoint reports the average change from baseline (Day 0) at Day 1 to Day 3. Day 0: the day before a participant started randomized treatment (if the GI threshold was reached 1 day previously) or the first day of randomized treatment if the threshold was reached that day. If the threshold was reached >1 day previously, then Day 0 is the last day when the threshold was reached, prior to the first dose. A negative change from baseline indicates that symptoms decreased. | The MITT: All participants who were randomized, received at least 1 dose of both DMF treatment and study treatment (montelukast or placebo) on/after the first DMF dose date, and had at least 1 GSRS score measurement during the Day 1 - Day 10 period. One participant in the MITT-Montelukast arm did not provide post-baseline data. | Posted | | Mean | Standard Deviation | units on scale | | Baseline (Day 0), Day 3 (72 hours after Day 0) | | | | ID | Title | Description |
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| OG000 | MITT-Placebo | Participants who reached the predefined threshold in scores on the GSRS during the Run-in Period entered the Study Treatment Period. Participants continued to receive 240 mg DMF twice daily and also received a montelukast-matching placebo tablet once daily by mouth for 8 weeks. Participants received only 240 mg DMF twice daily for 2 weeks after discontinuing treatment with placebo, then were followed for 2 additional weeks before a final phone interview. One participant randomized to placebo was excluded from the MITT. |
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| Secondary | Percentage of Participants Who Required GI Symptomatic Therapy During the Study | Symptomatic therapies were not permitted during the first 10 days after starting montelukast or placebo. From Day 10 onward, participants were allowed to use the following symptomatic therapies to treat DMF-related GI events: bismuth subsalicylate, simethicone, calcium carbonate, loperamide, proton-pump inhibitors and ondansetron. | The MITT: All participants who were randomized, received at least 1 dose of DMF treatment, received at least 1 dose of study treatment (montelukast or placebo) on/after the first DMF dose date, and had at least 1 GSRS score measurement during the Day 1 - Day 10 period. | Posted | | Number | | percentage of participants | | Day 10 to Week 10 | | | | ID | Title | Description |
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| OG000 | MITT-Placebo | Participants who reached the predefined threshold in scores on the GSRS during the Run-in Period entered the Study Treatment Period. Participants continued to receive 240 mg DMF twice daily and also received a montelukast-matching placebo tablet once daily by mouth for 8 weeks. Participants received only 240 mg DMF twice daily for 2 weeks after discontinuing treatment with placebo, then were followed for 2 additional weeks before a final phone interview. One participant randomized to placebo was excluded from the MITT. | | OG001 | MITT-Montelukast | Participants who reached the predefined threshold in scores on the GSRS during the Run-in Period entered the Study Treatment Period. Participants continued to receive 240 mg DMF twice daily and also received 10 mg of montelukast once daily by mouth for 8 weeks. Participants received only 240 mg DMF twice daily for 2 weeks after discontinuing treatment with montelukast, then were followed for 2 additional weeks before a final phone interview. |
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| Secondary | Percentage of Participants Who Discontinued DMF Therapy Due to GI-Related Adverse Events (AEs) From Day 0 to Week 10 | An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and that did not necessarily have a causal relationship with this treatment. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product. Participants used an electronic diary to record GI-related events. GI-related AEs included diarrhea, nausea, upper abdominal pain, abdominal pain, and dyspepsia. | The MITT: All participants who were randomized, received at least 1 dose of DMF treatment, received at least 1 dose of study treatment (montelukast or placebo) on/after the first DMF dose date, and had at least 1 GSRS score measurement during the Day 1 - Day 10 period. | Posted | | Number | | percentage of participants | | Day 0 to Week 10 | | | | ID | Title | Description |
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| OG000 | MITT-Placebo | Participants who reached the predefined threshold in scores on the GSRS during the Run-in Period entered the Study Treatment Period. Participants continued to receive 240 mg DMF twice daily and also received a montelukast-matching placebo tablet once daily by mouth for 8 weeks. Participants received only 240 mg DMF twice daily for 2 weeks after discontinuing treatment with placebo, then were followed for 2 additional weeks before a final phone interview. One participant randomized to placebo was excluded from the MITT. | | OG001 |
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| Secondary | Percentage of Participants Who Experienced AEs Related to Flushing | An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and that did not necessarily have a causal relationship with this treatment. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product. Flushing-related AEs included flushing and hot flush. Only events with an onset date on or after the date of first DMF dose (up to 27 days before Day 0) are presented. This includes events present before and subsequently worsened after the first dose of DMF. | The MITT: All participants who were randomized, received at least 1 dose of DMF treatment, received at least 1 dose of study treatment (montelukast or placebo) on/after the first DMF dose date, and had at least 1 GSRS score measurement during the Day 1 - Day 10 period. | Posted | | Number | | percentage of participants | | Day of first DMF dose (up to 27 days before Day 0) to Week 10 | | | | ID | Title | Description |
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| OG000 | MITT-Placebo | Participants who reached the predefined threshold in scores on the GSRS during the Run-in Period entered the Study Treatment Period. Participants continued to receive 240 mg DMF twice daily and also received a montelukast-matching placebo tablet once daily by mouth for 8 weeks. Participants received only 240 mg DMF twice daily for 2 weeks after discontinuing treatment with placebo, then were followed for 2 additional weeks before a final phone interview. One participant randomized to placebo was excluded from the MITT. |
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