ALVAIZ (eltrombopag tablets) Clinical Study Information
ALVAIZ was approved as a New Drug Application (NDA) through the 505(b)(2) pathway using Promacta®* (eltrombopag) as the reference listed drug (RLD).01
Study Design
A bioequivalence study was performed to assess the bioequivalence of eltrombopag choline (ALVAIZ) 54 mg tablets (“test product”) to Promacta®* (eltrombopag olamine) 75 mg tablets (RLD). The study was an open-label, randomized, single-dose, two-way crossover bioequivalence study in healthy adults (N=77). Participants were randomized to receive a single dose of either product under fasted conditions. There was a 14-day washout period between treatments. Pharmacokinetic (PK) samples were drawn from pre-dose to 72 hours post-dose.
Study Objectives
- Primary Objective: to assess the bioequivalence of eltrombopag choline 54 mg tablets (ALVAIZ) compared to that of Promacta (eltrombopag olamine) 75 mg tablets
- Secondary Objective: to assess the safety and tolerability of eltrombopag choline 54 mg tablets (ALVAIZ) and Promacta (eltrombopag olamine) 75 mg tablets
Study Results
Bioequivalence was established. Plasma concentrations between the 2 arms were similar, demonstrating bioequivalence between eltrombopag choline 54 mg tablets (ALVAIZ) and Promacta (eltrombopag olamine) 75 mg.
- Both products (i.e. “test” and RLD) were found to be safe and well tolerated.
- A total of four adverse events (AEs), two in each arm, were reported.
- All AEs were mild to moderate and resolved without any complications.
- There were no deaths in the study.
Additional studies showed similar in vitro dissolution profiles between eltrombopag choline 9 mg, 18 mg, 36 mg, and 54 mg tablets and Promacta (eltrombopag olamine) 12.5 mg, 25 mg, 50 mg, and 75 mg respectively, per the FDA requirements for the biowaiver of lower strengths.
Tablet Strength Bioequivalence Between ALVAIZ and Promacta
ALVAIZ Strength |
Promacta Strength |
|---|---|
| 9 mg tablet | 12.5 mg tablet |
| 18 mg tablet | 25 mg tablet |
| 36 mg tablet | 50 mg tablet |
| 54 mg tablet | 75 mg tablet |
The dose of ALVAIZ is not the same as other eltrombopag products. Do not change between ALVAIZ and other eltrombopag products unless advised by a healthcare provider.
IMPORTANT SAFETY INFORMATION
WARNINGS and PRECAUTIONS
Hepatic Decompensation in Patients with Chronic Hepatitis C. In patients with chronic hepatitis C, ALVAIZ in combination with interferon and ribavirin may increase the risk of hepatic decompensation.
Hepatotoxicity. ALVAIZ may increase the risk of severe and potentially life-threatening hepatotoxicity.
Increased Risk of Death and Progression of Myelodysplastic Syndromes to Acute Myeloid Leukemia. In a clinical trial of patients with intermediate to high risk MDS with thrombocytopenia, an increased number of progressions from MDS to AML was observed compared to placebo.
Thrombotic/Thromboembolic Complications may result from increases in platelet counts with ALVAIZ. Reported thrombotic/thromboembolic complications included both venous and arterial events and were observed at low and at normal platelet counts.
Cataracts. In clinical trials, development or worsening of cataracts was reported in patients treated with eltrombopag.
ADVERSE REACTIONS
The following clinically significant adverse reactions associated with ALVAIZ are described above.
- Hepatic Decompensation in Patients with Chronic Hepatitis C
- Hepatotoxicity
- Increased Risk of Death and Progression of Myelodysplastic Syndromes to Acute Myeloid Leukemia
- Thrombotic/Thromboembolic Complications
- Cataracts
Common adverse reactions associated with the use of ALVAIZ observed in placebo-controlled clinical trials in adults and pediatric patients include nausea, diarrhea, upper respiratory tract infection, nasopharyngitis, cough, anemia, pyrexia, and fatigue.
USE IN SPECIFIC POPULATIONS
Pregnancy and Lactation
There is insufficient data in pregnant women to assess any drug-associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes. Due to the potential for serious adverse reactions in a breastfed child from eltrombopag, breastfeeding is not recommended during treatment.
Pediatric Use
The safety and effectiveness of ALVAIZ have been established in pediatric patients 6 years and older with persistent or chronic ITP. The safety and effectiveness of ALVAIZ have not been established in pediatric patients less than 6 years of age with persistent or chronic ITP. The safety and effectiveness in pediatric patients with thrombocytopenia associated with chronic hepatitis C and refractory severe aplastic anemia have not been established.
INDICATIONS AND USAGE
Treatment of Thrombocytopenia in Patients with Persistent or Chronic Immune Thrombocytopenia
ALVAIZ® (eltrombopag tablets) are indicated for the treatment of thrombocytopenia in adult and pediatric patients 6 years and older with persistent or chronic immune thrombocytopenia (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. ALVAIZ should be used only in patients with ITP whose degree of thrombocytopenia and clinical condition increase the risk for bleeding.
Treatment of Thrombocytopenia in Patients with Hepatitis C Infection
ALVAIZ is indicated for the treatment of thrombocytopenia in adult patients with chronic hepatitis C to allow the initiation and maintenance of interferon-based therapy. ALVAIZ should be used only in patients with chronic hepatitis C whose degree of thrombocytopenia prevents the initiation of interferon-based therapy or limits the ability to maintain interferon-based therapy.
Treatment of Severe Aplastic Anemia
ALVAIZ is indicated for the treatment of adult patients with severe aplastic anemia who have had an insufficient response to immunosuppressive therapy.
Limitations of Use
- ALVAIZ is not indicated for the treatment of patients with myelodysplastic syndromes (MDS).
- Safety and efficacy have not been established in combination with direct-acting antiviral agents used without interferon for treatment of chronic hepatitis C infection.
Please see the full Prescribing Information, including Medication Guide and Boxed Warning.
*Promacta is a registered trademark of Novartis Pharma AG
References
-
Back to contents.
Data on File. [Clinical Study]