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| ID | Type | Description | Link |
|---|---|---|---|
| 2012-002566-12 | EudraCT Number |
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The primary objective of Parts 1 and 2 of the study were to establish the histologic effects of givinostat administered chronically at the selected daily dose.
The secondary objectives of Parts 1 and 2 of the study were as follows:
The primary objective of the Extension of the study was to evaluate the safety and tolerability of long-term administration of givinostat administered chronically at the selected daily dose in children with DMD.
The secondary objectives of the Extensions were:
This is a 2-part, phase II study to assess the effects of Givinostat on muscle histologic parameters and on clinical parameters in ambulant children with DMD.
The safety, tolerability, and pharmacokinetics of Givinostat will also be assessed.
Approximately 20 children were to be enrolled in the study as follows: the first 4 children were to be treated at a low dose level of givinostat (25 mg twice daily [BID] in children who weighed 20 kg to 49 kg and 37.5 mg BID in children who weighed ≥ 50 kg).
If none of the stopping criteria were met after 2 weeks of treatment at the low dose, the review team was to determine the escalated dose level (ie, intermediate dose level) to be used for the treatment of an additional 8 children who were to be treated at the intermediate dose. The 4 children previously treated at the low dose level were also switched to the intermediate dose level.
If none of the stopping criteria were met after 2 weeks of treatment at the intermediate dose, the review team was to determine the subsequent escalated dose level to be used for the treatment of an additional 8 children who were to be treated at the high dose. All children treated at the intermediate dose level were to be switched to the high dose level.
Once all 20 children enrolled during Part 1 of the study had been treated for at least 2 weeks, the review team was to determine the recommended dose (RD) to be used in Part 2 based on the safety and tolerability profile observed and on the pharmacokinetic (PK) analyses. All the children enrolled were switched to the RD level (37.5 mg BID), which was administered for the subsequent 12 months of the study (Part 2).
At the end of Part 2 of the study, parents were asked to consent and patients to assent to continuing their participation in the Extension to receive the study treatment at least until the final analysis was performed (Part 3-Extensions; after 52 months of treatment). The patients received givinostat at the same ongoing dose, during the last visit planned at 12 months, and were treated for additional 40 months (Extensions 1, 2, and 3 up to month 52).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Givinostat | Experimental | Givinostat will be administered as 2 oral doses daily while the child is in fed state. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Givinostat | Drug | Givinostat, oral suspension 10 mg/mL or oral capsules 50 mg, administered orally under fed conditions at the dose of 25 mg BID, 37.5 mg BID, and 50 mg BID during Part 1 for two weeks, and 25 mg BID and 37.5 mg BID during Part 2 for 12 months. Givinostat, oral suspension 10 mg/mL, administered orally under fed conditions at the dose of 25 mg BID or 37.5 mg BID during Extension 1, and modified as per patient's weight during Extensions 2 and 3 (up to 52 months). |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline to Part 2 in the Value of Muscle Fiber Area (MFA) % Comparing the Histology Biopsies Before and After 12 Months of Treatment With Givinostat. | The primary endpoint was the change in histology comparing the brachial biceps biopsies before and after ≥12 months of treatment with Givinostat. Muscle biopsies: A first brachial biceps biopsy (baseline) was taken prior to the first dose of study drug. A second brachial biceps biopsy was taken at Visit 10 (12 months) from the opposite arm. The muscle biopsy samples from the biceps muscle were collected by open biopsy. The minimum amount of muscle tissue required was a piece of muscle of at least 0.5 × 0.5 × 0.5 cm. | After12 months of treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline to End of Study in Cross Sectional Area (CSA) | This histological parameter was evaluated on the brachial biceps biopsies taken prior to the first dose of study drug and after 12 months of treatment with givinostat. | At 12 months |
| Change From Baseline to End of Study in Fibrosis, Necrosis, Fatty Replacement |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Enrico Bertini, MD | Bambino Gesù Children's Hospital, IRCCS, Rome, Italy. | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Azienda Ospedaliera Universitaria Policlinico G. Martino | Messina | 98125 | Italy | |||
| IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27566866 | Result | Bettica P, Petrini S, D'Oria V, D'Amico A, Catteruccia M, Pane M, Sivo S, Magri F, Brajkovic S, Messina S, Vita GL, Gatti B, Moggio M, Puri PL, Rocchetti M, De Nicolao G, Vita G, Comi GP, Bertini E, Mercuri E. Histological effects of givinostat in boys with Duchenne muscular dystrophy. Neuromuscul Disord. 2016 Oct;26(10):643-649. doi: 10.1016/j.nmd.2016.07.002. Epub 2016 Jul 11. |
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This is a single arm study and not a parallel group study. Patient enrollment occurred sequentially, until 20 patients were treated (part 1). For the entire design please refer to "detailed study description". Only demographics are reported by 3 Givinostat dose levels, while AEs and outcomes results are reported for the whole Givinostat population.
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| ID | Title | Description |
|---|---|---|
| FG000 | Givinostat | Givinostat will be administered as 2 oral doses daily while the child is in fed state. Givinostat: Givinostat, oral suspension 10 mg/mL or oral capsules 50 mg, administered orally under fed conditions at the dose of 25 mg BID, 37.5 mg BID, and 50 mg BID during Part 1 and 25 mg BID and 37.5 mg BID during Part 2. Givinostat, oral suspension 10 mg/mL, administered orally under fed conditions at the dose of 25 mg BID or 37.5 mg BID during Extension 1, and modified as per patient's weight during Extensions 2 and 3. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1 |
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| ||||||||||||||||||||||||
| Part 2 |
| |||||||||||||||||||||||||
| Extension 1 |
| |||||||||||||||||||||||||
| Extension 2 |
| |||||||||||||||||||||||||
| Extension 3 |
|
The ITT population included all children who were enrolled in the Part 1 portion or entered the Part 2 portion of the study. Patients were analyzed according to the dose level to which they were allocated. Twenty patients were included in the ITT population.
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| ID | Title | Description |
|---|---|---|
| BG000 | ITF2357 25 mg BID | Givinostat, oral suspension 10 mg/mL, administered orally under fed conditions at the dose of 25 mg BID, during Part 1 and 25 mg BID during Part 2 and during Extension 1. The dosage was modified as per patient's weight during Extensions 2 and 3. |
| BG001 | ITF2357 50 mg BID |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline to Part 2 in the Value of Muscle Fiber Area (MFA) % Comparing the Histology Biopsies Before and After 12 Months of Treatment With Givinostat. | The primary endpoint was the change in histology comparing the brachial biceps biopsies before and after ≥12 months of treatment with Givinostat. Muscle biopsies: A first brachial biceps biopsy (baseline) was taken prior to the first dose of study drug. A second brachial biceps biopsy was taken at Visit 10 (12 months) from the opposite arm. The muscle biopsy samples from the biceps muscle were collected by open biopsy. The minimum amount of muscle tissue required was a piece of muscle of at least 0.5 × 0.5 × 0.5 cm. | Evaluable population:all patients who received givinostat of at least 80% dose in Part 2, had at least 1 baseline and 1 post baseline biopsy and no major protocol violations. 19 Subjects completed Part 2, 1 subject was excluded by this analysis due to biopsy not readable. Results data are reported only for the "overall" Givinostat population. | Posted | Median | Full Range | percentage change | After12 months of treatment |
|
Adverse events (AE) were assessed throughout the study: in Part 1 (screen, weeks 0, 1, 2, 3, 4, 5); Part 2 (months 0, 1, 2, 3, 4.5, 6, 7.5, 9, 10.5,12); Extension 1 (months 14,16,18, 20, 22, 24, FU); Extension 2 (months 26,28, 30,32, 34, 36, FU); Extension 3 (months 40, 44, 48, 52, FU). Extensions 1, 2 and 3 together represent Part 3 of the study.
TEAEs by Primary System Organ Class, Preferred Term, and Relationship to Study Drug are reported for each dose separately in Part 1 and Part 2 of the study (i.e. Part 1 25.0 mg, Part 1 37.5 mg, Part 1 50 mg; Part 2 25.0 mg, Part 2 37.5 mg) and are reported to represent all participants and all parts of this study including the extension period altogether (i.e. Part 1 + Part 2 + Extensions 1, 2, and 3). Adverse events were not assessed by dose nor separately for the extension period.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Part 1 - 25 mg | The safety population included all children who received any investigational product. The dose level under which the patient was analyzed was the dose of investigational product that was actually received. 19 patients were included in the safety population of Part 1. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cushing's syndrome | Endocrine disorders | MedDRA (17.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA (17.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Paolo Bettica, MD | Italfarmaco SpA | +39 02 64431 | p.bettica@italfarmaco.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Aug 1, 2012 | Jan 22, 2020 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 10, 2018 | Jan 22, 2020 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D020388 | Muscular Dystrophy, Duchenne |
| D035583 | Rare Diseases |
| ID | Term |
|---|---|
| D009136 | Muscular Dystrophies |
| D020966 | Muscular Disorders, Atrophic |
| D009135 | Muscular Diseases |
| D009140 | Musculoskeletal Diseases |
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| ID | Term |
|---|---|
| C575255 | givinostat |
| C502418 | givinostat hydrochloride |
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|
|
These histological parameters were evaluated on the brachial biceps biopsies taken prior to the first dose of study drug and after 12 months of treatment with givinostat. |
| After 12 months |
| Change From Baseline to End of Study in Number of Hypercontracted Fibers | This histological parameter was evaluated on the brachial biceps biopsies taken prior to the first dose of study drug and after 12 months of treatment with givinostat. The number of fibers is calculated per microscopic field (20x). | At 12 months |
| Change From Baseline in Muscular Function After 12 Months of Treatment With Givinostat at the Selected Daily Dose Based on the 6-Minute Walk Test | This test measures the distance that a patient can quickly walk on a flat, hard surface in a period of 6 minutes. The 6-Minute Walk Test is a useful measure of functional capacity targeted at people with at least moderately severe impairment. The longer the walked distance the better the outcome. | At 12 months |
| Change From Baseline in Muscular Function After 12 Months of Treatment With Givinostat at the Selected Daily Dose Based on the North Star Ambulatory Assessment (NSAA) | The NSAA, which is composed by 17 items, was graded, for each item, using the standard scorecard with each assessment rated as 0 - unable to achieve independently, 1 - modified method but achieves goal independent of physical assistance from another, or 2 - normal with no obvious modification of activity. The subscales scores are summed up to compute a total score, ranging from 0 to 34. The higher the total score, the better the outcome. The mean Change From Baseline to EoS in NSAA total score is reported hereunder. | At 12 months |
| Change From Baseline in Muscular Function After 12 Months of Treatment With Givinostat at the Selected Daily Dose Based on the Performance of Upper Limb (PUL) | The PUL (version 1.2) was used to assess the change in motor performance of the upper limb over time in patients with Becker and Duchenne muscular dystrophy, from when they are still ambulant, until they loose all arm function when non-ambulant. The revised version of the PUL included 22 items. These include one entry item to define the starting functional level, and 21 items subdivided into:
| At 12 months |
| Change From Baseline in Muscular Function After After 24 (Extension 1), 36 (Extension 2), and 52 Months (Extension 3) of Treatment With Givinostat at the Selected Daily Dose Based on the 6-Minute Walk Test | This test measures the distance that a patient can quickly walk on a flat, hard surface in a period of 6 minutes. The 6-Minute Walk Test is a useful measure of functional capacity targeted at people with at least moderately severe impairment. The longer the walked distance the better the outcome. | At 24, 36, and 52 months |
| Change From Baseline in Muscular Function After 24 (Extension 1), 36 (Extension 2), and 52 Months (Extension 3) of Treatment With Givinostat at the Selected Daily Dose Based on the North Star Ambulatory Assessment (NSAA) | The NSAA, which is composed by 17 items, was graded, for each item, using the standard scorecard with each assessment rated as 0 - unable to achieve independently, 1 - modified method but achieves goal independent of physical assistance from another, or 2 - normal with no obvious modification of activity. The subscales scores are summed up to compute a total score, ranging from 0 to 34. The higher the total score, the better the outcome. The mean Change From Baseline to EoS in NSAA total score is reported hereunder. | At 24, 36, and 52 months |
| Change From Baseline in Muscular Function After 24 (Extension 1), 36 (Extension 2), and 52 Months (Extension 3) of Treatment With Givinostat at the Selected Daily Dose Based on the Performance of Upper Limb (PUL) | The PUL (version 1.2) was used to assess the change in motor performance of the upper limb over time in patients with Becker and Duchenne muscular dystrophy, from when they are still ambulant, until they loose all arm function when non-ambulant. The revised version of the PUL included 22 items taking. These include one entry item to define the starting functional level, and 21 items subdivided into:
| At 24, 36, and 52 months |
| Number of Children Experiencing Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Type and Severity of TEAEs | Summary of Treatment-emergent Adverse Events (TEAE) Reporting from Baseline to the End of Extension 3 (Month 52). In the analysis were included: Any TEAE, Any treatment-related TEAE, Any mild or moderate or severe TEAE, Any life-threatening or disabling TEAE, Any TEAE resulting in death, any serious adverse event, and Any TEAE resulting in study discontinuation. | Part 1, Part 2, and Extensions 1, 2, and 3 |
| Milan |
| 20122 |
| Italy |
| Policlinico Agostino Gemelli | Roma | 00168 | Italy |
| Ospedale Pediatrico Bambino Gesù | Rome | 00165 | Italy |
|
Givinostat oral capsules 50 mg, administered orally under fed conditions at the dose of 50 mg BID during Part 1. The dosage was modified as per patient's weight during Extensions 2 and 3. |
| BG002 | ITF2357 37.5 mg BID | Givinostat, oral suspension 10 mg/mL, administered orally under fed conditions at the dose of 37.5 mg BID during Part 1 and 37.5 mg BID during Part 2 and during Extension 1. The dosage was modified as per patient's weight during Extensions 2 and 3. |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG000 | Overall | Givinostat was administered as 2 oral doses daily while the child is in fed state. Givinostat, oral suspension 10 mg/mL or oral capsules 50 mg, was administered at the dose of 25 mg BID, 37.5 mg BID, and 50 mg BID during Part 1, and 25 mg BID and 37.5 mg BID during Part 2. |
|
|
|
| Secondary | Change From Baseline to End of Study in Cross Sectional Area (CSA) | This histological parameter was evaluated on the brachial biceps biopsies taken prior to the first dose of study drug and after 12 months of treatment with givinostat. | The ITT population included all children who were enrolled in the Part 1 or entered the Part 2 of the study. For histology parameters patients were analyzed "overall" for Givinostat population. 19 completed part 2 but only 18 subejcts had 2 biopsies readable | Posted | Mean | Standard Deviation | μm2 | At 12 months |
|
|
|
|
| Secondary | Change From Baseline to End of Study in Fibrosis, Necrosis, Fatty Replacement | These histological parameters were evaluated on the brachial biceps biopsies taken prior to the first dose of study drug and after 12 months of treatment with givinostat. | The ITT population included all children who were enrolled in the Part 1 or entered the Part 2 of the study. For histology parameters patients were analyzed "overall" for Givinostat population. 19 Subjects completed Part 2 but only 18 had 2 biopsies readable. | Posted | Mean | Standard Deviation | percentage of total area | After 12 months |
|
|
|
| Secondary | Change From Baseline to End of Study in Number of Hypercontracted Fibers | This histological parameter was evaluated on the brachial biceps biopsies taken prior to the first dose of study drug and after 12 months of treatment with givinostat. The number of fibers is calculated per microscopic field (20x). | The ITT population included all children who were enrolled in the Part 1 or entered the Part 2 of the study. For histology parameters patients were analyzed "overall" for Givinostat population.19 Subjects completed Part 2 but only 18 had 2 biopsies readable. | Posted | Mean | Standard Deviation | number of fibers | At 12 months |
|
|
|
| Secondary | Change From Baseline in Muscular Function After 12 Months of Treatment With Givinostat at the Selected Daily Dose Based on the 6-Minute Walk Test | This test measures the distance that a patient can quickly walk on a flat, hard surface in a period of 6 minutes. The 6-Minute Walk Test is a useful measure of functional capacity targeted at people with at least moderately severe impairment. The longer the walked distance the better the outcome. | The ITT population included all children who were enrolled in the Part 1 portion or entered the Part 2 portion of the study. Results data are reported only for the "overall" Givinostat population, due to a small sample. 19 subjects completed Part 2 of the study 19 but only 18 performed the 6-Minute Walk Test | Posted | Mean | Standard Deviation | meters | At 12 months |
|
|
|
| Secondary | Change From Baseline in Muscular Function After 12 Months of Treatment With Givinostat at the Selected Daily Dose Based on the North Star Ambulatory Assessment (NSAA) | The NSAA, which is composed by 17 items, was graded, for each item, using the standard scorecard with each assessment rated as 0 - unable to achieve independently, 1 - modified method but achieves goal independent of physical assistance from another, or 2 - normal with no obvious modification of activity. The subscales scores are summed up to compute a total score, ranging from 0 to 34. The higher the total score, the better the outcome. The mean Change From Baseline to EoS in NSAA total score is reported hereunder. | The ITT population included all children who were enrolled in the Part 1 portion or entered the Part 2 portion of the study. Patients were analyzed "overall" due to a small sample size. Although different Givinostat dose levels were administered, results data are reported only for the "overall" Givinostat population | Posted | Mean | Standard Deviation | score on a scale | At 12 months |
|
|
|
| Secondary | Change From Baseline in Muscular Function After 12 Months of Treatment With Givinostat at the Selected Daily Dose Based on the Performance of Upper Limb (PUL) | The PUL (version 1.2) was used to assess the change in motor performance of the upper limb over time in patients with Becker and Duchenne muscular dystrophy, from when they are still ambulant, until they loose all arm function when non-ambulant. The revised version of the PUL included 22 items. These include one entry item to define the starting functional level, and 21 items subdivided into:
| The ITT population included all children who were enrolled in the Part 1 portion or entered the Part 2 portion of the study. Patients were analyzed overall, due to a small sample size. Although different Givinostat dose levels were administered, results data are reported only for the "overall" Givinostat population. | Posted | Mean | Standard Deviation | score on a scale | At 12 months |
|
|
|
| Secondary | Change From Baseline in Muscular Function After After 24 (Extension 1), 36 (Extension 2), and 52 Months (Extension 3) of Treatment With Givinostat at the Selected Daily Dose Based on the 6-Minute Walk Test | This test measures the distance that a patient can quickly walk on a flat, hard surface in a period of 6 minutes. The 6-Minute Walk Test is a useful measure of functional capacity targeted at people with at least moderately severe impairment. The longer the walked distance the better the outcome. | The ITT population included all children who were enrolled in the Part 1 portion or entered the Part 2 portion of the study. Patients were analyzed overall, due to a small sample size. Although different Givinostat dose levels were administered, results data are reported only for the "overall" Givinostat population. | Posted | Mean | Standard Deviation | meters | At 24, 36, and 52 months |
|
|
|
| Secondary | Change From Baseline in Muscular Function After 24 (Extension 1), 36 (Extension 2), and 52 Months (Extension 3) of Treatment With Givinostat at the Selected Daily Dose Based on the North Star Ambulatory Assessment (NSAA) | The NSAA, which is composed by 17 items, was graded, for each item, using the standard scorecard with each assessment rated as 0 - unable to achieve independently, 1 - modified method but achieves goal independent of physical assistance from another, or 2 - normal with no obvious modification of activity. The subscales scores are summed up to compute a total score, ranging from 0 to 34. The higher the total score, the better the outcome. The mean Change From Baseline to EoS in NSAA total score is reported hereunder. | The ITT population included all children who were enrolled in the Part 1 portion or entered the Part 2 portion of the study. Patients were analyzed overall due to a small sample size. Although different Givinostat dose levels were administered, results data are reported only for the "overall" Givinostat population. | Posted | Mean | Standard Deviation | score on a scale | At 24, 36, and 52 months |
|
|
|
| Secondary | Change From Baseline in Muscular Function After 24 (Extension 1), 36 (Extension 2), and 52 Months (Extension 3) of Treatment With Givinostat at the Selected Daily Dose Based on the Performance of Upper Limb (PUL) | The PUL (version 1.2) was used to assess the change in motor performance of the upper limb over time in patients with Becker and Duchenne muscular dystrophy, from when they are still ambulant, until they loose all arm function when non-ambulant. The revised version of the PUL included 22 items taking. These include one entry item to define the starting functional level, and 21 items subdivided into:
| The ITT population included all children who were enrolled in the Part 1 portion or entered the Part 2 portion of the study. Patients were analyzed overall due to a small sample size. Although different Givinostat dose levels were administered, results data are reported only for the "overall" Givinostat population. | Posted | Mean | Standard Deviation | score on a scale | At 24, 36, and 52 months |
|
|
|
| Secondary | Number of Children Experiencing Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Type and Severity of TEAEs | Summary of Treatment-emergent Adverse Events (TEAE) Reporting from Baseline to the End of Extension 3 (Month 52). In the analysis were included: Any TEAE, Any treatment-related TEAE, Any mild or moderate or severe TEAE, Any life-threatening or disabling TEAE, Any TEAE resulting in death, any serious adverse event, and Any TEAE resulting in study discontinuation. | The safety population included all children who received any investigational product. Although different Givinostat dose levels were administered, results data are reported only for the "overall" Givinostat population. During the extension period the dosage was adjusted by patient weight | Posted | Number | participants | Part 1, Part 2, and Extensions 1, 2, and 3 |
|
|
|
| 0 |
| 4 |
| 0 |
| 4 |
| 3 |
| 4 |
| EG001 | Part 1 - 50 mg | The safety population included all children who received any investigational product. The dose level under which the patient was analyzed was the dose of investigational product that was actually received. 19 patients were included in the safety population of Part 1. | 0 | 12 | 1 | 12 | 12 | 12 |
| EG002 | Part 1 - 37.5 mg | The safety population included all children who received any investigational product. The dose level under which the patient was analyzed was the dose of investigational product that was actually received. 19 patients were included in the safety population of Part 1. | 0 | 7 | 0 | 7 | 6 | 7 |
| EG003 | Part 2 - 37.5 mg | The safety population included all children who received any investigational product. The dose level under which the patient was analyzed was the dose of investigational product that was actually received. 19 patients were included in the safety population of Part 2. | 0 | 19 | 1 | 19 | 19 | 19 |
| EG004 | Part 2 - 25 mg | The safety population included all children who received any investigational product. The dose level under which the patient was analyzed was the dose of investigational product that was actually received. 19 patients were included in the safety population of Part 2. | 0 | 12 | 1 | 12 | 12 | 12 |
| EG005 | Overall (Part 1 + Part 2 + Extensions 1, 2, 3 ) | The safety population included all children who received any investigational product. The dose level under which the patient was analyzed was the dose of investigational product that was actually received. 19 patients were included in the safety population of Part 1 and 19 patients were included in the safety population of Part 2. In all Extensions, the Safety Analysis Population was set up to 20 patients (100%), including all patients who received any investigational product. | 0 | 20 | 8 | 20 | 20 | 20 |
| Cataracts | Eye disorders | MedDRA (17.0) | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA (17.0) | Systematic Assessment |
|
| Femural fracture | Injury, poisoning and procedural complications | MedDRA (17.0) | Systematic Assessment |
|
| Lower limb fracture | General disorders | MedDRA (17.0) | Systematic Assessment |
|
| Platelet count decreased | Investigations | MedDRA (17.0) | Systematic Assessment |
|
| Rhabdomyolysis | Musculoskeletal and connective tissue disorders | MedDRA (17.0) | Systematic Assessment |
|
| Haematuria | Renal and urinary disorders | MedDRA (17.0) | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA (17.0) | Systematic Assessment |
|
| Cardiac discomfort | Cardiac disorders | MedDRA (17.0) | Systematic Assessment |
|
| Extrasystoles | Cardiac disorders | MedDRA (17.0) | Systematic Assessment |
|
| Left ventricular dilatation | Cardiac disorders | MedDRA (17.0) | Systematic Assessment |
|
| Left ventricular disfunction | Cardiac disorders | MedDRA (17.0) | Systematic Assessment |
|
| Palpitations | Cardiac disorders | MedDRA (17.0) | Systematic Assessment |
|
| Sinus tachycardia | Cardiac disorders | MedDRA (17.0) | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA (17.0) | Systematic Assessment |
|
| Ventricular extrasystoles | Cardiac disorders | MedDRA (17.0) | Systematic Assessment |
|
| Gilbert's syndrome | Congenital, familial and genetic disorders | MedDRA (17.0) | Systematic Assessment |
|
| Ear pain | Ear and labyrinth disorders | MedDRA (17.0) | Systematic Assessment |
|
| Adrenal insufficiency | Endocrine disorders | MedDRA (17.0) | Systematic Assessment |
|
| Autoimmune thyroiditis | Endocrine disorders | MedDRA (17.0) | Systematic Assessment |
|
| Delayed puberty | Endocrine disorders | MedDRA (17.0) | Systematic Assessment |
|
| Hypothyroidism | Endocrine disorders | MedDRA (17.0) | Systematic Assessment |
|
| Secondary adrenocartical insufficiency | Endocrine disorders | MedDRA (17.0) | Systematic Assessment |
|
| Cataract | Eye disorders | MedDRA (17.0) | Systematic Assessment |
|
| Lens discoloration | Eye disorders | MedDRA (17.0) | Systematic Assessment |
|
| Lenticular opacity | Eye disorders | MedDRA (17.0) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
|
| Colitis | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
|
| Faeces soft | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
|
| Frequent bowel movements | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
|
| Haemorrhoids | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA (17.0) | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA (17.0) | Systematic Assessment |
|
| Gait disturbance | General disorders | MedDRA (17.0) | Systematic Assessment |
|
| Non cardiac chest pain | General disorders | MedDRA (17.0) | Systematic Assessment |
|
| Peripheral swelling | General disorders | MedDRA (17.0) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (17.0) | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
|
| Ear infection | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
|
| Gastrointestinal viral infection | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
|
| Molluscum contagiosum | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
|
| Paronychia | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
|
| Pharyngitis | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
|
| Respiratory tract infection | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
|
| Rhinitis | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
|
| Tooth infection | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
|
| Varicella | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA (17.0) | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA (17.0) | Systematic Assessment |
|
| Femur fracture | Injury, poisoning and procedural complications | MedDRA (17.0) | Systematic Assessment |
|
| Foot fracture | Injury, poisoning and procedural complications | MedDRA (17.0) | Systematic Assessment |
|
| Head injury | Injury, poisoning and procedural complications | MedDRA (17.0) | Systematic Assessment |
|
| Joint injury | Injury, poisoning and procedural complications | MedDRA (17.0) | Systematic Assessment |
|
| Laceration | Injury, poisoning and procedural complications | MedDRA (17.0) | Systematic Assessment |
|
| Legament injury | Injury, poisoning and procedural complications | MedDRA (17.0) | Systematic Assessment |
|
| Legament sprain | Injury, poisoning and procedural complications | MedDRA (17.0) | Systematic Assessment |
|
| Limb injury | Injury, poisoning and procedural complications | MedDRA (17.0) | Systematic Assessment |
|
| Lower limb fracture | Injury, poisoning and procedural complications | MedDRA (17.0) | Systematic Assessment |
|
| Muscle strain | Injury, poisoning and procedural complications | MedDRA (17.0) | Systematic Assessment |
|
| Spinal compression fracture | Injury, poisoning and procedural complications | MedDRA (17.0) | Systematic Assessment |
|
| Spinal cord injury sacral | Injury, poisoning and procedural complications | MedDRA (17.0) | Systematic Assessment |
|
| Tendon injury | Injury, poisoning and procedural complications | MedDRA (17.0) | Systematic Assessment |
|
| Tibia fracture | Injury, poisoning and procedural complications | MedDRA (17.0) | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | MedDRA (17.0) | Systematic Assessment |
|
| Intraocular pressure increased | Investigations | MedDRA (17.0) | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | MedDRA (17.0) | Systematic Assessment |
|
| Platelet count decreased | Investigations | MedDRA (17.0) | Systematic Assessment |
|
| White blood cell count decreased | Investigations | MedDRA (17.0) | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (17.0) | Systematic Assessment |
|
| Hypertryglyceridaemia | Metabolism and nutrition disorders | MedDRA (17.0) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (17.0) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (17.0) | Systematic Assessment |
|
| Fracture pain | Musculoskeletal and connective tissue disorders | MedDRA (17.0) | Systematic Assessment |
|
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA (17.0) | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (17.0) | Systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA (17.0) | Systematic Assessment |
|
| Osteopenia | Musculoskeletal and connective tissue disorders | MedDRA (17.0) | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (17.0) | Systematic Assessment |
|
| Tendinous contracture | Musculoskeletal and connective tissue disorders | MedDRA (17.0) | Systematic Assessment |
|
| Tendon pain | Musculoskeletal and connective tissue disorders | MedDRA (17.0) | Systematic Assessment |
|
| Tendonitis | Musculoskeletal and connective tissue disorders | MedDRA (17.0) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (17.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (17.0) | Systematic Assessment |
|
| Haematuria | Renal and urinary disorders | MedDRA (17.0) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (17.0) | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (17.0) | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (17.0) | Systematic Assessment |
|
| Laryngeal inflammation | Respiratory, thoracic and mediastinal disorders | MedDRA (17.0) | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (17.0) | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (17.0) | Systematic Assessment |
|
| Pharyngeal erythema | Respiratory, thoracic and mediastinal disorders | MedDRA (17.0) | Systematic Assessment |
|
| Dermatosis | Skin and subcutaneous tissue disorders | MedDRA (17.0) | Systematic Assessment |
|
| Ecchymosis | Skin and subcutaneous tissue disorders | MedDRA (17.0) | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA (17.0) | Systematic Assessment |
|
| Erythema annulare | Skin and subcutaneous tissue disorders | MedDRA (17.0) | Systematic Assessment |
|
| Intertrigo | Skin and subcutaneous tissue disorders | MedDRA (17.0) | Systematic Assessment |
|
| Nail dystrophy | Skin and subcutaneous tissue disorders | MedDRA (17.0) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (17.0) | Systematic Assessment |
|
| Seborrhoeic dermatitis | Skin and subcutaneous tissue disorders | MedDRA (17.0) | Systematic Assessment |
|
| Skin lesion | Skin and subcutaneous tissue disorders | MedDRA (17.0) | Systematic Assessment |
|
| Solar dermatitis | Skin and subcutaneous tissue disorders | MedDRA (17.0) | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA (17.0) | Systematic Assessment |
|
Not provided
Not provided
| D009468 | Neuromuscular Diseases |
| D009422 | Nervous System Diseases |
| D040181 | Genetic Diseases, X-Linked |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| Title | Measurements |
|---|---|
|
| Fatty replacement |
|
| Necrosis |
|
|
| Extension 3 |
|
|
| Title | Measurements |
|---|---|
|
|
| Extension 3 |
|
|
| Title | Measurements |
|---|---|
|
| Any moderate TEAE |
|
| Any severe TEAE |
|
| Any life-threatening or disabling TEAE |
|
| Ant TEAE resulting in death |
|
| Any SAE |
|
| Any TEAE resulting in study discontinuation |
|