Drug Trials Snapshots: RAPIBLYK
HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the key clinical trials that supported the original FDA approval of this drug, and whether there were differences among sex, race, age, and ethnic 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 healthcare provider about the benefits and risks of a drug.
Some of the information in this Snapshot is for presentation purposes and does not represent the approved conditions of use of this drug. Refer to the RAPIBLYK Prescribing Information for all the approved conditions of use of this drug (e.g., indication(s), population(s), dosing regimen(s), safety information).
Snapshots are limited to the information available at the time of the original approval of the drug and do not provide information on who participated in clinical trials that supported later approvals for additional uses of the drug (if applicable).
RAPIBLYK (landiolol hydrochloride)
RAP-ee-blik
AOP Orphan Pharmaceuticals AG
Approval date: November 22, 2024
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
RAPIBLYK is a beta-adrenergic blocker indicated for the short-term reduction of ventricular rate in adults with supraventricular tachycardia including atrial fibrillation and atrial flutter.
How is this drug used?
RAPIBLYK is an intravenous infusion that is taken continuously in a monitored setting.
Who participated in the clinical trials?
The FDA approved RAPIBLYK based on evidence from 8 published clinical trial(s) of 1192 patients with supraventricular tachycardia, including atrial fibrillation, and atrial flutter (see Table 1). The trials(s) were conducted at over 95 sites in 2 countries (China and Japan). All 8 randomized controlled trials were used to assess both safety and effectiveness, and all patients were enrolled outside of the United States.
The number of patients representing efficacy findings differs from the number of patients representing safety due to different pools of study participants analyzed for efficacy and safety.
How were the trials designed?
ROf the 8 published clinical trials, 5 were randomized, double blind, and placebo controlled with a primary endpoint of heart rate decrease after 10 minutes of RAPIBLYK administration. Heart rate decrease was defined by the following criteria: 1) greater than 20% decrease; 2) heart rate that dropped to less than 100 beats per minute; or 3) at least intermittent cessation of the arrhythmia.
The 3 supportive clinical trials were randomized, double blind, and either placebo controlled with a primary endpoint of heart rate decrease after 5 minutes, or active controlled with digoxin or diltiazem administration and a primary endpoint after 24 to 72 hours.
DEMOGRAPHICS SNAPSHOT
Table 1. Common Baseline Attributes of the Clinical Trial Populations, Efficacy Population
Trial | Comparator | Mean Age (years) | Sex (% male) | Weight (kg) | Systolic Blood Pressure (mmHg) | Heart Rate (beats per minute) | % Supraventricular arrythmia |
1 (n=99) | Placebo | 61.9 ± 11.4 | 65% | 60.5 ± 9.5 | 125.4 ± 20.6 | 117.3 ± 25.8 | 80% Atrial fibrillation 20% Atrial flutter |
2 (n=275) | Placebo | 60.8 | 56% | - | 139.9 | 78-105: 40% 106-115: 36% 116-162: 24% | 97% Sinus rhythm 3% ‘other’ |
3 (n=54) | Placebo | 58.3 ± 13.4 | 65% | 58.8 ± 12.7 | 161.4 ± 26.9 | 112.1 ± 9.3 | 89% Sinus rhythm 7% Atrial tachycardia |
4 (n=12) | Placebo | 71.2 | 58% | 53.0 | 142.9 | 130.2 | 58% Sinus rhythm 42% Atrial tachycardia |
5 (n=151) | Placebo | 63.5 | 74% | - | 128.9 | 133.9 | 62% Sinus rhythm 34% Atrial fibrillation or atrial flutter |
6 (n=71) | Diltiazem | 70.2 ± 10.6 | 68% | - | 116 ± 26 | 129 ± 20 | 100% Atrial fibrillation or atrial flutter |
7 (n=200) | Digoxin | 71.6 ± 11.5 | 53% | 60.5 ± 13.2 | 125.7 ± 21.8 | 138.1 ± 15.3 | 87% Atrial fibrillation 12% Atrial flutter |
8 (n=240) | Placebo | 44.2 ± 11.5 | 30% | 59.2 ± 9.4 | 120 ± 18 | 109 ± 8 | Unknown |
Source: Adapted from FDA Review
Figure 1. Baseline Demographics by Sex, Efficacy Population
Source: Adapted from FDA Review
What are the benefits of this drug?
RAPIBLYK reduced heart rate in patients with an arrhythmia known as supraventricular tachycardia, including atrial fibrillation and atrial flutter.
What are the benefits of this drug (results of trials used to assess efficacy)?
In the 5 randomized, double-blind, placebo-controlled studies, treatment of 317 adults with supraventricular tachycardia resulted in a decreased heart rate, as per criteria defined above, in 40-90% of patients treated with landiolol within about 10 minutes from start of therapy, compared to 0-11% of patients who received placebo (see Table 2). The infused dose of landiolol in these studies ranged from 9.3 to 74.6 mcg/kg/min (equivalent to 10 to 80 mcg/kg/min landiolol hydrochloride).
TABLE 2. Summary of landiolol effectiveness on the primary endpoint in placebo-controlled trials
Study | Proportion of Patients Achieving Moderate Improvement of Tachycardia (Full-Analysis Set) | Proportion of Patients Achieving Moderate Improvement of Tachycardia (Per-Protocol Set) | Differences in Response Rates between Analysis Sets as Reported in the Publication | ||
Landiolol | Placebo | Landiol | Placebo | ||
1 | Not reported | Not reported | 60% (n = 45) | 2% (n = 44) | Not applicable. Full-Analysis Set not reported. |
2 | 79% (n = 136) | 9% (n = 139) | 80% (n = 117) | 9% (n = 127) | No difference in response rates between Analysis Sets. |
3 | 89% (n = 27) | 11% (n = 27) | 86% (n = 21) | 10% (n = 20) | No difference in response rates between Analysis Sets. |
4 | 51% (n = 98) | 0 (n = 96) | Not reported | Not reported | Per-Protocol Set not reported in detail but reported as similar to the Full-Analysis Set. |
5 | 75% (n = 8) | 0 (n = 4) | Not reported | Not reported | Not applicable. Per-Protocol Set not reported. |
Source: FDA Reviewer’s Analysis
Abbreviations: n, number of subjects
Were there any differences in how well the drug worked in clinical trials among sex, race, and age?
Subgroup results were not available, as none were provided in this literature-based submission.
What are the possible side effects?
The safety evaluation of Landiolol injection was derived from 19 placebo-controlled clinical trials involving 1,761 patients (in a variety of clinical in-patient settings) with supraventricular tachycardia or at high risk for supraventricular tachycardia. The most important and common adverse reaction is hypotension, which occurred in approximately 10% of patients receiving RAPIBLYK vs. 1% in those receiving placebo in the randomized controlled clinical trials.
Were there any differences in side effects among sex, race, and age?
Subgroup results were not available, as none were provided in this literature-based submission.
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.