Safety Study of Crushed Deferasirox Film Coated Tablets in Pediatric Patients With Transfusional Hemosiderosis

To assess the safety of crushed deferasirox FCT with respect to selected gastrointestinal (GI) disorders (esophagitis, stomatitis, mouth ulceration, gastric ulcers, haemorrhage, abdominal pain, diarrhea, nausea, and vomiting). Only descriptive analysis performed.

Time frame: Baseline (Week 1 Day 1) up to Week 24, plus 30 day safety follow-up.

Population: Safety set

Absolute change from baseline over time in body temperature measurements was to be provided. Only descriptive analysis performed.

Time frame: Baseline (BL), Week 2, Week 3, Week 4, Week 8, Week 12, Week 16, Week 20, EOT (Week 24)

Population: Safety set. For each parameter, only patients with a value at both baseline and post baseline were to be included.

Absolute change from baseline over time in body weight measurements was to be provided. Only descriptive analysis performed.

Time frame: Baseline (BL), Week 4, Week 8, Week 12, Week 16, Week 20, EOT (Week 24)

Population: Safety set. For each parameter, only patients with a value at both baseline and post baseline were to be included.

Absolute change from baseline over time in supine pulse rate was to be provided. Only descriptive analysis performed.

Time frame: Baseline (BL), Week 2, Week 3, Week 4, Week 8, Week 12, Week 16, Week 20, EOT (Week 24)

Population: Safety set. For each parameter, only patients with a value at both baseline and post baseline were to be included.

Absolute change from baseline over time in SF values up to 24 weeks of treatment were to be provided. Only descriptive analysis performed.

Time frame: Baseline (BL), Week 4, Week 8, Week 12, Week 16, EOT (Week 24)

Population: Full Analysis Set (FAS)

Absolute change from baseline over time in systolic and diastolic blood pressures measurements were to be provided. Only descriptive analysis performed.

Time frame: Baseline (BL), Week 2, Week 3, Week 4, Week 8, Week 12, Week 16, Week 20, EOT (Week 24)

Population: Safety set. For each parameter, only patients with a value at both baseline and post baseline were to be included.

Analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event TEAEs and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters. Only descriptive analysis performed.

Time frame: Baseline (Week 1 Day 1) up to Week 24, plus 30 day safety follow-up.

Population: Safety set

The GI symptom score was calculated from responses to 5 questions, each with a possible score of 1 to 5, for an overall possible score range of 5 to 25, where a lower score represents a less severe GI symptom and a higher score represents a more severe GI symptom. GI symptom scores were summarized using descriptive statistics at week 2, week 3, week 4, week 8, week 12, week 16, week 20 and EOT.

Time frame: Week 2, Week 3, Week 4, Week 8, Week 12, Week 16, Week 20, EOT (Week 24)

Population: Full Analysis Set (FAS). Only patients with a value at both baseline and post baseline were to be included.

The GI symptom score was calculated from responses to 5 questions, each with a possible score of 1 to 5, for an overall possible score range of 5 to 25, where a lower score represents a less severe GI symptom and a higher score represents a more severe GI symptom. GI symptom scores were summarized using descriptive statistics at week 2, week 3, week 4, week 8, week 12, week 16, week 20 and EOT.

Time frame: Week 2, Week 3, Week 4, Week 8, Week 12, Week 16, Week 20, EOT (Week 24)

Population: Full Analysis Set (FAS). Only patients with a value at both baseline and post baseline were to be included.

The mSICT questionnaire was to be completed at screening visit 1, week 4, week 12 and EOT. The responses from screening visit 1 for mSICT questionnaire were to be considered as baseline. The modified SICT consisted of 20 items that represented 3 domains: Adherence, Preference and Concerns. The mSICT adherence domain consisted of 6 items from the child's perspective and 6 items from the caregiver's perspective, each with a possible score of 1 to 5, for an overall possible score range of 6 to 30. A higher score indicates poorer adherence. Only descriptive analysis performed.

Time frame: Week 4, Week 12, EOT (Week 24)

Population: Full Analysis Set (FAS). Only patients with a value at both baseline and post baseline were to be included.

The mSICT questionnaire was to be completed at screening visit 1, week 4, week 12 and EOT. The responses from screening visit 1 for mSICT questionnaire were to be considered as baseline. The modified SICT consisted of 20 items that represented 3 domains: Adherence, Preference and Concerns. The mSICT concerns domain scale for child's response had a possible range from 2 to 10, based on two questions and the mSICT concerns domain scale for caregiver's responses had the possible range of 1 to 5 based on one question. A higher score indicated fewer concerns. Only descriptive analysis performed.

Time frame: Week 4, Week 12, EOT (Week 24)

Population: Full Analysis Set (FAS). Only patients with a value at both baseline and post baseline were to be included.

The mSICT questionnaire was to be completed at screening visit 1, week 4, week 12 and EOT. The responses from screening visit 1 for mSICT questionnaire were to be considered as baseline. The modified SICT consisted of 20 items that represented 3 domains: Adherence, Preference and Concerns. The mSICT preference domain consisted of 3 items including the rank of the medicine (tablet to dissolve in liquid, tablet taken once a day, tablet taken 3 times a day, tablet crushed, sprinkle powder on food and injection), with a range of 1 to 6 (1 being most preferred and 6 being least preferred), based on what the child prefers. These items were presented descriptively using frequency counts.

Time frame: Week 4, Week 12, EOT (Week 24)

Population: Full Analysis Set (FAS). Only patients with a value at both baseline and post baseline were to be included.

The mSICT questionnaire was to be completed at screening visit 1, week 4, week 12 and EOT. The responses from screening visit 1 for mSICT questionnaire were to be considered as baseline. The modified SICT consisted of 20 items that represented 3 domains: Adherence, Preference and Concerns. The mSICT preference domain consisted of 3 items including the reason child preferred crushed medicine (taste, aftertaste, convenience, number of pills, no/less side effects, can correctly prepare the medicine, easier to remember to take the medicine, number of times he/she has to take the medicine, no/less pain on the injection site, gain personal time with their family and friends, and other). These items were presented descriptively using frequency counts.

Time frame: Week 4, Week 12, EOT (Week 24)

Population: Full Analysis Set (FAS). Only patients with a value at both baseline and post baseline were to be included.

The mSICT questionnaire was to be completed at screening visit 1, week 4, week 12 and EOT. The responses from screening visit 1 for mSICT questionnaire were to be considered as baseline. The modified SICT consisted of 20 items that represented 3 domains: Adherence, Preference and Concerns. The mSICT preference domain consisted of 3 items including the type of medicine the child said he/she liked best (tablet to dissolve in liquid, tablet (taken once a day), tablet (taken 3 times a day), tablet crushed, sprinkle powder on food, injection and I don't know). These items were presented descriptively using frequency counts.

Time frame: Week 4, Week 12, EOT (Week 24)

Population: Full Analysis Set (FAS). Only patients with a value at both baseline and post baseline were to be included.

The mSICT questionnaire was to be completed at screening visit 1, week 4, week 12 and EOT. The responses from screening visit 1 for mSICT questionnaire were to be considered as baseline. The modified SICT consisted of 20 items that represented 3 domains: Adherence, Preference and Concerns. The mSICT adherence domain consisted of 6 items from the child's perspective and 6 items from the caregiver's perspective, each with a possible score of 1 to 5, for an overall possible score range of 6 to 30. A higher score indicates poorer adherence. Only descriptive analysis performed.

Time frame: Week 4, Week 12, EOT (Week 24)

Population: Full Analysis Set (FAS). Only patients with a value at both baseline and post baseline were to be included.

The mSICT questionnaire was to be completed at screening visit 1, week 4, week 12 and EOT. The responses from screening visit 1 for mSICT questionnaire were to be considered as baseline. The modified SICT consisted of 20 items that represented 3 domains: Adherence, Preference and Concerns. The mSICT concerns domain scale for child's response had a possible range from 2 to 10, based on two questions and the mSICT concerns domain scale for caregiver's responses had the possible range of 1 to 5 based on one question. A higher score indicated fewer concerns. Only descriptive analysis performed.

Time frame: Week 4, Week 12, EOT (Week 24)

Population: Full Analysis Set (FAS). Only patients with a value at both baseline and post baseline were to be included.

The mSICT questionnaire was to be completed at screening visit 1, week 4, week 12 and EOT. The responses from screening visit 1 for mSICT questionnaire were to be considered as baseline. The modified SICT consisted of 20 items that represented 3 domains: Adherence, Preference and Concerns. The mSICT preference domain consisted of 3 items including the rank of the medicine (tablet to dissolve in liquid, tablet taken once a day, tablet taken 3 times a day, tablet crushed, sprinkle powder on food and injection), with a range of 1 to 6 (1 being most preferred and 6 being least preferred), based on what the child prefers. These items were presented descriptively using frequency count.

Time frame: Baseline (BL), Week 4, Week 12, EOT (Week 24)

Population: Full Analysis Set (FAS). Only patients with a value at both baseline and post baseline were to be included.

The mSICT questionnaire was to be completed at screening visit 1, week 4, week 12 and EOT. The responses from screening visit 1 for mSICT questionnaire were to be considered as baseline. The modified SICT consisted of 20 items that represented 3 domains: Adherence, Preference and Concerns. The mSICT preference domain consisted of 3 items including the reason child preferred crushed medicine (taste, aftertaste, convenience, number of pills, no/less side effects, can correctly prepare the medicine, easier to remember to take the medicine, number of times he/she has to take the medicine, no/less pain on the injection site, gain personal time with their family and friends, and other). These items were presented descriptively using frequency counts.

Time frame: Baseline (BL), Week 4, Week 12, EOT (Week 24)

Population: Full Analysis Set (FAS). Only patients with a value at both baseline and post baseline were to be included.

The mSICT questionnaire was to be completed at screening visit 1, week 4, week 12 and EOT. The responses from screening visit 1 for mSICT questionnaire were to be considered as baseline. The modified SICT consisted of 20 items that represented 3 domains: Adherence, Preference and Concerns. The mSICT preference domain consisted of 3 items including the type of medicine the child said he/she liked best (tablet to dissolve in liquid, tablet (taken once a day), tablet (taken 3 times a day), tablet crushed, sprinkle powder on food, injection and I don't know). These items were presented descriptively using frequency counts.

Time frame: Baseline (BL), Week 4, Week 12, EOT (Week 24)

Population: Full Analysis Set (FAS). Only patients with a value at both baseline and post baseline were to be included.

The palatability (taste and ability to consume medicine) questionnaire consisted of 4 items, three items measuring taste or ability to consume medicine and one item measuring aftertaste. The aftertaste item was treated as a separate item and scored on a 5-point response scale with the response format Very good = 1 (best), Good = 2, Neither good nor bad = 3, Bad = 4, Very bad = 5 (worst). Only descriptive analysis performed using frequency counts.

Time frame: Week 4, Week 12, EOT (Week 24)

Population: Full Analysis Set (FAS). Only patients with a value at both baseline and post baseline were to be included.

The palatability (taste and ability to consume medicine) questionnaire consisted of 4 items, three items measuring taste or ability to consume medicine and one item measuring aftertaste. The aftertaste item was treated as a separate item and scored on a 5-point response scale with the response format Very good = 1 (best), Good = 2, Neither good nor bad = 3, Bad = 4, Very bad = 5 (worst). Only descriptive analysis performed using frequency counts.

Time frame: Baseline, Week 4, Week 12, EOT (Week 24)

Population: Full Analysis Set (FAS). Only patients with a value at both baseline and post baseline were to be included.

Safety measured by notable post-baseline changes in Auditory assessments (comprehensive audiometry threshold examination and speech recognition). Baseline was defined as the last non-missing value on or prior to the first dose. Only descriptive analysis performed.

Time frame: Baseline (Week 1 Day 1) up to Week 24, plus 30 day safety follow-up.

Population: Safety set. For each parameter, only patients with a value at both baseline and post baseline were to be included.

Safety measured by notable post-baseline changes in Ocular assessments (Distance visual acuity test, Applanation tonometry, lens photography, wide angle fundus photography of the retina and optic nerve). Ocular assessment were required at screening and end of Treatment; during treatment, they were to be performed at the discretion of the investigator based on patient reporting symptoms. Baseline was defined as the last non-missing value on or prior to the first dose. Only descriptive analysis performed.

Time frame: Baseline (Week 1 Day 1) up to Week 24, plus 30 day safety follow-up.

Population: Safety set. For each parameter, only patients with a value at both baseline and post baseline were to be included.

The GI symptom questionnaire consisted of 6 items, 5 of which were scored using a 1-5 rating scale. The sixth item assessed bowel movement frequency during the past week, using 7 response options 0 = 0 (None), 1 = 1, 2 = 2, 3 = 3, 4 = 4, 5 = 5 - 10 and 6 = 11 or more. The GI bowel movements item score was presented descriptively using frequency counts.

Time frame: Week 2, Week 3, Week 4, Week 8, Week 12, Week 16, Week 20, EOT (Week 24)

Population: Full Analysis Set (FAS). Only patients with a value at both baseline and post baseline were to be included.

The GI symptom questionnaire consisted of 6 items, 5 of which were scored using a 1-5 rating scale. The sixth item assessed bowel movement frequency during the past week, using 7 response options 0 = 0 (None), 1 = 1, 2 = 2, 3 = 3, 4 = 4, 5 = 5 - 10 and 6 = 11 or more. The GI bowel movements item score was presented descriptively using frequency counts.

Time frame: Baseline, Week 2, Week 3, Week 4, Week 8, Week 12, Week 16, Week 20, EOT (Week 24)

Population: Full Analysis Set (FAS). Only patients with a value at both baseline and post baseline were to be included.

Safety measured by the notable post-baseline changes in ECG values (PR, QRS, QT, QTcF and HR intervals) compared to baseline. Baseline was defined as the last non-missing value on or prior to the first dose. Only descriptive analysis performed.

Time frame: Baseline (Week 1 Day 1) up to Week 24, plus 30 day safety follow-up.

Population: Safety set. For each parameter, only patients with a value at both baseline and post baseline were to be included.

Safety measured by the worst post-baseline severity grade observed in a patient calculated using the normal/low/high classifications based on local laboratory normal ranges, regardless of the baseline status. Baseline was defined as the last non-missing value on or prior to the first dose. The selected chemistry parameters were: Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), Aspartate aminotransferase (AST), total bilirubin, direct bilirubin, serum creatinine and Urine protein creatinine ratio (UPCR) (Protein/Creatinine represented UPCR). Only descriptive analysis performed.

Time frame: Baseline (Week 1 Day 1) up to Week 24, plus 30 day safety follow-up.

Population: Safety Set

The palatability (taste and ability to consume medicine) questionnaire consisted of 4 items, three items measuring taste or ability to consume medicine and one item measuring aftertaste. The aftertaste item was treated separately. Among the taste items, first one measured taste on a five point response scale. The last two items measured what happened after taking the medicine, i.e., swallowed or vomited etc. and how the perceived amount of liquid taken with the medicine was, enough, not enough or too much. The palatability summary score was calculated from these three items using a scoring matrix and the score ranges from 0 to 11. A higher score indicates better palatability. Only descriptive analysis was performed.

Time frame: Week 4, Week 12, EOT (Week 24)

Population: Full Analysis Set (FAS). Only patients with a value at both baseline and post baseline were to be included.

The palatability (taste and ability to consume medicine) questionnaire consisted of 4 items, three items measuring taste or ability to consume medicine and one item measuring aftertaste. The aftertaste item was treated separately. Among the taste items, first one measured taste on a five point response scale. The last two items measured what happened after taking the medicine, i.e., swallowed or vomited etc. and how the perceived amount of liquid taken with the medicine was, enough, not enough or too much. The palatability summary score was calculated from these three items using a scoring matrix and the score ranges from 0 to 11. A higher score indicates better palatability. Only descriptive analysis was performed.

Time frame: Week 4, Week 12, EOT (Week 24)

Population: Full Analysis Set (FAS). Only patients with a value at both baseline and post baseline were to be included.