Drugs

Drug Trials Snapshots: RYDAPT

HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the clinical trials that supported the FDA approval of this drug, and whether there were differences among sex, race, and age groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.

LIMITATIONS OF THIS SNAPSHOT:
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your health provider about the risks and benefits of a drug. Refer to RYDAPT Prescribing Information for complete information.

RYDAPT (midostaurin)
rye-dapt
Novartis Pharmaceuticals Corp.
Approval date: April 28, 2017


DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

RYDAPT is used to treat adults with acute myeloid leukemia (AML) that has a mutation in a gene called FLT3, in combination with chemotherapy.

AML is a rapidly progressing cancer that forms in the bone marrow and results in an increased number of white blood cells in the bloodstream.

How is this drug used?

RYDAPT is a capsule. Two capsules (total of 50 mg) are taken two times a day with food.

What are the benefits of this drug?

In the trial, patients who received RYDAPT in combination with chemotherapy lived longer than patients who received chemotherapy alone. A specific median survival could not be reliably estimated.

What are the benefits of this drug (results of trials used to assess efficacy)?

The table below summarizes efficacy results established on the basis of overall survival (OS), measured from the date of randomization until death by any cause.

Figure 4. Kaplan-Meier Curve for Overall Survival

Figure summarizes efficacy results for the clinical trial.

RYDAPT Prescribing Information

Were there any differences in how well the drug worked in clinical trials among sex, race and age?

  • Sex: RYDAPT worked similarly in men and women.
  • Race: Differences in how well the drug worked among patients of different races could not be determined due to unknown race in majority of patients.
  • Age: RYDAPT worked similarly in patients younger and older than 40 years of age.

Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?

The table below summarizes efficacy results based on OS by age, sex, and race. These analyses were exploratory and therefore should be interpreted with caution.

Table 2. Overall Survival by Demographic Subgroup

ParameterSubgroupRYDAPTPlaceboHazard ratio* [95% CI]
Age18-39 years43/9745/950.70 [0.46, 1.06]
40-60 years128/262141/2610.80 [0.63, 1.02]
SexWomen93/18697/2121.01 [0.76, 1.34]
Men78/17489/1450.53 [0.39, 0.72]
RaceWhite82/14774/1280.87 [0.64, 1.20]
All Other89/213112/2290.69 [0.53, 0.92]

* Hazard ratio estimated by Cox regression model, stratified by FLT mutation status
Note: overall survival not censored for stem cell transplantation
CI = confidence interval

Adapted from FDA Statistical review

What are the possible side effects?

RYDAPT can cause serious lung toxicity and harm to unborn baby.

Common side effects of RYDAPT are low white blood cell counts with fever (febrile neutropenia), nausea, ulcers or redness inside the mouth (mucositis), vomiting, headache, bruising, muscle or bone pain, nose bleeds, device-related infection, high blood sugar levels, and upper respiratory tract infection.

What are the possible side effects (results of trials used to assess safety)?

The tables below summarize adverse reactions and laboratory abnormalities in the clinical trial.

Table 3. Common Adverse Reactions (≥ 10% Incidence and ≥ 2% More Frequent on RYDAPT) of Patients with AML

Adverse ReactionsAll GradesGrades ≥ 3
RYDAPT + chemo
n=2291
%
Placebo + chemo
n=2261
%
RYDAPT + chemo
n=3451
%
Placebo + chemo
n=3351
%
Gastrointestinal disorders
Nausea8370610
Mucositisa66621113
Vomiting615335
Hemorrhoids151110
Blood and lymphatic system disorders
Febrile neutropenia83818483
Petechiae362711
Nervous system disorders
Headachea463833
Musculoskeletal and connective tissue disorders
Musculoskeletal paina333152
Arthralgia148< 1< 1
Respiratory, thoracic and mediastinal disorders
Epistaxis282431
Infections and infestations
Device-related infection24171610
Upper respiratory tract infectiona201543
Investigations
Hyperglycemiaa201776
Activated partial thromboplastin time prolonged13832
Skin and subcutaneous tissue disorders
Hyperhidrosis14800
Renal and urinary disorders
Renal insufficiencya12953
Psychiatric disorders
Insomnia1280< 1

1 For trial sites in North America, only Grades 3 and 4 were collected.
a based on grouping of individual PTs:

  • Upper respiratory tract infections: e.g. nasopharyngitis, upper respiratory tract infections, sinusitis
  • Mucositis: e.g. radiation mucositis, stomatitis, laryngeal pain
  • Musculoskeletal pain: e.g. back pain, bone pain, pain in extremity
  • Renal insufficiency: e.g. blood creatinine increased, renal failure, acute kidney injury
  • Hyperglycemia: mainly hyperglycemia

RYDAPT Prescribing Information

Table 4. New or Worsening Laboratory Abnormalities (≥ 10% Incidence and ≥ 2% More Frequent on RYDAPT) Reported in Patients with AML

Laboratory AbnormalityRYDAPT
N=345
All Grades
%
RYDAPT
N=345
Grade 3/4
%
Placebo
N=335
All Grades
%
Placebo
N=335
Grade 3/4
%
Alanine aminotransferase (ALT) increased71206916
Hypernatremia211152
Hypocalcemia747708

RYDAPT Prescribing Information

Were there any differences in side effects among sex, race and age?

  • Sex: The occurrence of side effects was similar in men and women.
  • Race: Differences in side effects among patients of different races could not be determined due to unknown race in majority of patients.
  • Age: The occurrence of side effects was similar in patients younger and older than 40 years of age.

Were there any differences in side effects of the clinical trials among sex, race, and age groups?

Tables below summarize adverse events during the clinical trials by sex, and age subgroup. Racial subgroup differences were not investigated as race was unknown or not reported for majority of patients.

These analyses were exploratory and therefore should be interpreted with caution.

Table 5. Subgroup Analysis of Adverse Events by Sex

 Men
N=91
n (%)
Women
N=51
n (%)
Any grade event91 (100)51(100)
Grade ≥3 event76 (84)43 (84)
Any SAE65 (71)32 (63)
Grade ≥3 SAE60 (66)30 (59)

SAE=serious adverse event

Table 7. Subgroup Analysis of Adverse Events by Age

 Age < 65 Years
N=78
n (%)
Age ≥ 65 Years
N=64
n (%)
Any grade event78 (100)64 (100)
Grade ≥3 event64 (82)55 (86)
Any SAE55 (71)42 (66)
Grade ≥3 SAE49 (63)41 (64)

SAE=serious adverse event

Adapted from Clinical trial report

WHO WAS IN THE CLINICAL TRIALS?

Who participated in the clinical trials?

The FDA approved RYDAPT based on evidence from one clinical trial of 717 patients with newly-diagnosed AML. The selected patients had to have a certain type of mutation (FLT3-mutation) which was confirmed using an FDA-approved test.

The trial was conducted at 177 centers across 13 countries in Europe, North America, and Australia.

Figure 1 summarizes how many men and women were in the clinical trial.

Figure 1. Baseline Demographics by Sex

Pie chart summarizing how many men and women were in the clinical trial. In total, 319 men (44%) and 398 women (56%) participated in the clinical trial

Adapted from FDA Statistical review

Figure 2 and Table 1 below summarize the percentage of patients by race in the clinical trial.

Figure 2. Baseline Demographics by Race

Pie chart summarizing the percentage of patients by race enrolled in the clinical trial. In total, 275 Whites (38%), 37 Other (5%) and 405 unknown(57%) participated in the clinical trial.

Adapted from FDA Statistical review

Table 1. Baseline Demographics by Race

RaceNumber of PatientsPercentage
White27538
Black or African American172
Asian132
American Indian or Alaska Native1less than 1
Mixed3less than 1
Not reported3less than 1
Unknown*40557

* some countries where the trial was conducted do not allow for the collection of this type of data

Adapted from FDA Statistical review

Figure 3 summarizes how many patients of certain age were enrolled in the clinical trial.

Figure 3. Baseline Demographics by Age

Pie chart summarizing how many individuals of certain age groups were in the clinical trial. In total, 192 patients were below 40 years old (27%) and 525 were 40 -60 years old (73%).

Adapted from FDA Statistical review

Who participated in the trials?

The table below summarizes demographics of all patients enrolled in the clinical trial.

Table 8. Baseline Demographics of Patients Enrolled in the Clinical Trial

 RYDAPT (N=360)
n (%)
Placebo (N=357)
n (%)
Total (N=717)
n (%)
Sex
Men174 (48)145 (41)319 (45)
Women186 (52)212 (60)398 (55)
Age (years)
Min, Max19, 5918, 6018, 60
Median474847
Age Group (years)
18-3997 (27)95 (27)192 (27)
40-60263 (73)262 (73)525 (73)
Race
White147 (41)128 (36)275 (38)
Black or African American8 (2)9 (3)17 (2)
Asian8 (2)5 (1)13 (2)
American Indian or Alaska Native01 (<1)1 (<1)
Mixed race2 (1)1 (<1)3 (<1)
Not reported1 (<1)2 (<1)3 (<1)
Unknown*194 (54)211 (57)405 (56)
Ethnicity
Hispanic or Latino9 (3)7 (2)16 (2)
Non Hispanic or Latino103 (29)107 (30)210 (29)
Not reported2 (1)1 (<1)3 (<1)
Unknown*246 (68)238 (67)484 (68)
Missing04 (1)4 (1)
Geographic Region
North America121 (34)115 (32)236 (33)
Other239 (66)242 (68)481 (67)

* some countries where the trial was conducted do not allow for the collection of this type of data
Adapted from FDA Statistical review

How were the trials designed?

There was one trial that evaluated the benefit and side effects of RYDAPT. All patients had newly-diagnosed AML with confirmed FLT3-mutation and no previous treatments. Patients received either RYDAPT or placebo two times per day on days 8 to 21 of each cycle of chemotherapy. Neither the patients nor the health care providers knew whether RYDAPT or placebo was given until the end of the trial.

The benefit of RYDAPT was evaluated by measuring overall survival (OS), from the date of randomization until death by any cause. The assessment of benefit was done after a minimum follow-up of approximately 3.5 years after the trial entry of the last patient.

How were the trials designed?

The safety and efficacy of RYDAPT were established in one randomized, double-blind placebo-controlled trial that enrolled 717 patients with newly-diagnosed FLT3-mutated AML.

Patients were randomized (1:1) to receive RYDAPT 50 mg or placebo twice daily on days 8 to 21 of each cycle of induction and consolidation chemotherapy. Patients who were in complete remission at the end of consolidation chemotherapy could receive RYDAPT 50 mg or placebo twice daily in continuous 28-day cycles as monotherapy for up to an additional 12 months.

The efficacy was established on the basis of overall survival (OS), measured from the date of randomization until death by any cause. The primary analysis was conducted after a minimum follow-up of approximately 3.5 years after the randomization of the last patient.

GLOSSARY

CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.

PRESCRIBING INFORMATION

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Page Last Updated: 05/09/2017
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