Open-label, Multicenter Study Assessing Preference for Deferasirox Film-coated Tablet Compared to Dispersible Tablet

NCT02993224 | Completed Phase 2 Results

• 2 other identifiers: CICL670FIC052016-002282-61
• Study Type: interventional
• Target: 148
• Locations: 7 countries
• Sites: 17

Brief Summary

Study to evaluate patient preference of deferasirox film-coated tablet (FCT) or deferasirox dispersible tablet (DT) in patient with transfusion - dependent thalassemia or non-transfusion -dependent thalassemia as measured by preference questionnaire at Week 48

Conditions

Transfusion-dependent Thalassemia; Non-transfusion-dependent Thalassemia

Keywords

thalassemia; TDT; transfusion-dependent; non-transfusion-dependent; NTDT

Outcome Measures

Primary Outcomes (1)

• Number of Participants Preferring Deferasirox FCT or DT at Week 48 Based on Preference Questionnaire (Item 2)

  Number of participants preferring deferasirox FCT or DT as measured by preference questionnaire (item 2) at Week 48. The preference questionnaire was a 3-item questionnaire. At Week 48, the second item of the preference questionnaire asked the patients (or parents of young patients from 2 to 9 years old) which medicine did the patient "like best": "Tablet to dissolve in liquid" (=deferasirox DT), "Film coated tablet" (=deferasirox FCT), "Sprinkle powder on food" (=deferasirox FCT) and "I don't know" (=none of the above). The number of participants who selected each response option for item 2 was assessed. The analysis was performed for participants who answered the item 2 of the preference questionnaire.

  Week 48

Secondary Outcomes (11)

• Number of Participants Preferring Deferasirox FCT, Deferasirox DT or Previous Iron Chelation Therapy at Week 28 Based on Preference Questionnaire (Item 2)

  Week 28

• Number of Participants Preferring Deferasirox DT or Previous Iron Chelation Therapy at Week 4 and Week 24 Based on Preference Questionnaire (Item 2)

  Week 4 and Week 24

• Number of Participants Selecting Each Reason for Treatment Preference as Assessed by the Preference Questionnaire at Week 28 and Week 48

  Week 28 and Week 48

• Percentage of Consumed Tablet Counts During Deferasirox DT and Deferasirox FCT Treatment Periods

  Deferasirox DT: From Baseline up to Week 24. Deferasirox FCT: From Week 25 up to Week 48

• Change Over Time in Aftertaste Score of Palatability Questionnaire

  Week 4, 24, 28 and 48

Study Arms (1)

Deferasirox DT followed by deferasirox FCT

EXPERIMENTAL

Participants were treated with deferasirox DT followed by deferasirox FCT (core phase). Those who entered the extension phase were treated with deferasirox FCT

Drug: Deferasirox dispersable tablet (DT); Drug: Deferasirox film coated tablet (FCT)

Interventions

Deferasirox dispersable tablet (DT) DRUG

Deferasirox DT was provided as 125 mg, 250 mg, 500 mg dispersible tablets for oral use. The strengths provided in an individual country could differ and reflected the strengths available commercially in each country. For iron chelation naive participants, the starting dose on Baseline Day 1 was 20 mg/kg/day in TDT and 10 mg/kg/day in NTDT. For iron chelation (deferoxamine and/or deferiprone) pre-treated participants, the starting dose was equivalent to the dose of deferoxamine received (for participants pre-treated with deferoxamine) and based on their serum ferritin levels (for participants pre-treated with deferiprone). Participants took deferasirox DT once daily for 24 weeks (core phase). The required number of deferasirox DT tablets were to be dispersed with gentle stirring in a glass of water.

Deferasirox DT followed by deferasirox FCT

Deferasirox film coated tablet (FCT) DRUG

Deferasirox FCT was provided as 90 mg, 180 mg, 360 mg film coated tablets for oral use. The FCT starting dose on Week 25 was 14 mg/kg/day in TDT and 7 mg/kg/day in NTDT. Participants took deferasirox FCT once daily for 24 weeks during the core phase and up to 48 weeks during the extension phase. For patients with difficulties in swallowing deferasirox FCT, it was allowed to crush the film-coated tablets and administer the study drug by sprinkling the full dose on soft food (like yogurt or apple puree).

Deferasirox DT followed by deferasirox FCT

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Prior to any screening procedures were performed, written informed consent/assent must be provided. For pediatric patients, consent was obtained from parent(s) or legal patient's representative. Investigators also obtained assent of patients according to local, regional or national guidelines.
• Male and female patient aged ≥ 2 years
• Deferasirox naïve patient or chelated naive patient or treated by other chelators for at least 6 months, such as:
• Deferiprone/ DFP
• Deferoxamine /DFO
• Combination (DFO + DFP)
• Subject was willing to discontinue current iron chelation therapy at least 5 days prior to study day 1 and for the duration of the study
• Patients with transfusion-dependent thalassemia (independent of underlying condition) with transfusional iron overload as shown by a serum ferritin level of \> 1000 ng/ml at screening and if available, LIC \> 3 mg Fe/g dw within 6 months prior to screening
• Patients with non-transfusion-dependent thalassemia with iron overload as shown by a serum ferritin level of ≥ 800 ng/ml at screening and if available, LIC ≥ 5 mg Fe/g dw within 6 months prior to screening

You may not qualify if:

• Creatinine clearance below the contraindication limit in the locally approved prescribing information.
• Serum creatinine level \> 1.5 x ULN (upper limit of normal)
• AST (SGOT) /ALT (SGPT) \> 5 x ULN, unless LIC confirmed as \>10 mg Fe/dw within 6 months prior to screening visit.
• Significant proteinuria as indicated by a urinary protein/creatinine ratio \> 0.5 mg/mg in a non-first void urine sample.
• Patients with significant impaired gastrointestinal (GI) function or GI disease that might significantly alter the absorption of oral deferasirox (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
• Clinical or laboratory evidence of active Hepatitis B or Hepatitis C (HBsAg in the absence of HBsAb OR HCV Ab positive with HCV RNA positive).
• Patients with psychiatric or addictive disorders which prevent them from giving their informed consent or undergoing any of the treatment options or patients unwilling or unable to comply with the protocol
• Patients with a known history of HIV seropositivity (Elisa or Western blot).
• History of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin.
• Patients participating in another clinical trial or receiving an investigational drug. Patients who have recently completed treatment with an investigational product must have ceased this treatment for at least five times the half-life of the investigational product.
• History of hypersensitivity to any of the study drug or excipients.
• Significant medical condition interfering with the ability to partake in this study (e.g. systemic uncontrolled hypertension, unstable cardiac disease not controlled by standard medical therapy, systemic disease (cardiovascular, renal, hepatic, etc.).
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they were using effective methods of contraception during dosing of study treatment
• Women were considered post-menopausal and not of child bearing potential if they had had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or had had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman had been confirmed by follow up hormone level assessment is she considered not of child bearing potential.
• Sexually active males unless they used a condom during intercourse while taking drug and for 28 days after stopping study medication and should not father a child in this period. A condom was required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (17)

Novartis Investigative Site

Alexandria, 21131, Egypt

Location

Novartis Investigative Site

Cairo, 11562, Egypt

Location

Novartis Investigative Site

Zagazig, 44519, Egypt

Location

Novartis Investigative Site

Hazmiyeh, Beyrouth, PO BOX 213, Lebanon

Location

Novartis Investigative Site

Rabat, 10102, Morocco

Location

Novartis Investigative Site

Al Ahsa, SAU, Saudi Arabia

Location

Novartis Investigative Site

Jeddah, 21159, Saudi Arabia

Location

Novartis Investigative Site

Jeddah, 21589, Saudi Arabia

Location

Novartis Investigative Site

Riyadh, 11117, Saudi Arabia

Location

Novartis Investigative Site

Bangkok Noi, Bangkok, 10700, Thailand

Location

Novartis Investigative Site

Bangkoknoi, Bangkok, 10700, Thailand

Location

Novartis Investigative Site

Bangkok, 10400, Thailand

Location

Novartis Investigative Site

Ankara, 06100, Turkey (Türkiye)

Location

Novartis Investigative Site

Antalya, 07070, Turkey (Türkiye)

Location

Novartis Investigative Site

Istanbul, 34093, Turkey (Türkiye)

Location

Novartis Investigative Site

Hanoi, Vietnam

Location

Novartis Investigative Site

Ho Chi Minh City, DISTRICT 1, Vietnam

Location

MeSH Terms

Conditions

Thalassemia

Interventions

Deferasirox

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Benzoates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Study director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

862-778-8300

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2016
• First Posted: December 15, 2016
• Study Start: July 27, 2017
• Primary Completion: January 29, 2020
• Study Completion: March 11, 2021
• Last Updated: October 4, 2021
• Results First Posted: October 4, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will share

Locations

LE (1); TU (3); SA (4); VN (2); EG (3); MO (1); TH (3)