CYNAPSUS CTH-301
Research type
Research Study
Full title
An Open-Label, Phase 3 Study Examining the Long-Term Safety, Tolerability and Efficacy of APL-130277 in Levodopa Responsive Patients with Parkinson's Disease Complicated by Motor Fluctuations ( "OFF" Episodes)
IRAS ID
201528
Contact name
Ray Chaudhuri
Contact email
Sponsor organisation
Cynapsus Therapeutics Inc
Eudract number
2016-000637-43
Clinicaltrials.gov Identifier
Duration of Study in the UK
1 years, 0 months, 1 days
Research summary
Up to 50% of Parkinson’s disease patients experience daily changes in the ability to perform motor activities, called “OFF” episodes. These include periods of time where their L-Dopa medication wears off before the next dose or when their L-Dopa medications suddenly, unexpectedly stop working. When people with Parkinson’s disease are properly medicated and their stiffness, slowness and walking are improved, they are said to be “ON”.
The drug that is currently available to help and quickly manage people experiencing “OFF” episodes is called apomorphine, under the brand name APO-go in the UK, which is given as an injection under the skin.
APO-go is the first and only prescription medicine that reverses “OFF” episodes (wearing off of medications before the next dose of L-Dopa and unpredictable, unexpected episodes where your medication stops working) associated with advancing Parkinson’s disease. Within 8-20 minutes of injection, apomorphine shows the ability to switch the patient with Parkinson's disease to the “ON” state. The effect of a single injection under the skin lasts for 60-90 minutes.
Cynapsus is developing the study drug called APL-130277, a fast-acting thin film formulation of apomorphine that is placed under the tongue and is intended to be an alternative to the injectable form of apomorphine.
The goal of this development program, however, is to formulate a medication that provides the PD patient with an easier delivery system. It is hypothesized that an orally available formulation will be easier to use, allow quicker control over predicted “OFF” periods, be more readily accessible to the patient when unpredicted “OFF” episodes occur during activities of daily living, and potentially be used by the milder PD patient when “OFF” episodes begin during the advancement of the disease.
"The objective is to evaluate the long-term safety and tolerability and efficacy of APL-130277 in patients with Parkinson’s Disease (PD) over a 24 week period".________________________________________
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Sent: 05 October 2023 10:28:00 (UTC+00:00) Dublin, Edinburgh, Lisbon, London
To: Approvals
Subject: Final report submission - 05/10/2023Form: Submit your Final Report
Lay summary of study results: This is a summary of the side effects the participants had during this trial. Side effects, which are also known as “adverse events”, are unwanted or unexpected medical problems that can happen when someone takes a medication. An adverse event is considered “serious” when it is life threatening, causes lasting problems, or requires hospital care. These adverse events may or may not have been caused by the trial drug. A lot of research is needed to know whether a treatment causes an adverse event.
Of the 496 participants in the trial, there were 449 who met with trial doctors regularly during the first few weeks so that their dose of APL-130277 could be adjusted. During this dose-adjustment period:
• 232 of the 449 participants (51.7% of this group) had at least 1 adverse event
• 6 participants (1.3%) had at least 1 serious adverse event
• 1 participant (0.2%) died due to an adverse event
• 30 participants (6.7%) stopped treatment with APL-130277 because of an adverse event
These were the serious adverse events that happened during this part of the trial:
• 1 participant (0.2% of this group) had a type of irregular heartbeat called atrial fibrillation
• 1 participant (0.2%) broke their sternum (breastbone)
• 1 participant (0.2%) had a type of brain tumor called a glioblastoma
• 1 participant (0.2%) had a blockage in the neck of their bladder (the spot where urine leaves the bladder on its way out of the body)
• 1 participant (0.2%) had a blood clot in a vein
• 1 participant (0.2%) died due to drowning
The most common adverse event during this part of the trial was nausea. There were 67 participants (14.9% of this group) who reported nausea during this part of the trial. This was the only adverse event that happened to at least 10% of participants in this part of the trial. There were other adverse events, but they happened to fewer participants.
Of the 496 participants in the trial, there were 426 who started long-term treatment with a stable dose of APL-130277. During this long-term treatment period:
• 365 of the 426 participants (85.7% of this group) had at least 1 adverse event
• 58 participants (13.6%) had at least 1 serious adverse event
• 7 participants (1.6%) died due to an adverse event
• 145 participants (34%) stopped treatment with APL-130277 because of an adverse event
These were the most common serious adverse events (events that happened to more than 2 participants) during this part of the trial:
• 5 participants (1.2% of this group) had pneumonia, which is a type of lung infection
• 5 participants (1.2%) had a fall
• 4 participants (0.9%) had a bladder infection
• 3 participants (0.7%) had a heart attack
• 3 participants (0.7%) had heart failure
• 3 participants (0.7%) had back pain
There were other serious adverse events during this part of the trial, but they happened to fewer participants.
These were the serious adverse events that led to death during this part of the trial:
• 2 participants (0.5% of this group) died due to pneumonia
• 1 participant (0.2%) died due to aspiration pneumonia (a type of lung infection caused by breathing in something besides air, such as food, liquid, or vomit)
• 1 participant (0.2%) died due to pneumonia with cardio-respiratory arrest (a sudden loss of heart and lung function)
• 1 participant (0.2%) died due to complications of an infection
• 1 participant (0.2%) died due to a heart attack
• 1 participant (0.2%) died due to drowning
The most common adverse events during this part of the trial were nausea and falling. There were 91 participants (21.4% of this group) who reported nausea and 44 participants (10.3%) who reported having a fall. These were the only adverse events that happened to at least 10% of participants in this part of the trial. There were other adverse events, but they happened to fewer participants.REC name
London - Riverside Research Ethics Committee
REC reference
16/LO/0542
Date of REC Opinion
12 May 2016
REC opinion
Further Information Favourable Opinion