Date: 2014-11-19
Type of information: Results
phase: 2
Announcement: results
Company: Cynapsus Therapeutics (Canada)
Product: APL-130277
Action
mechanism: APL-130277 is a patented apomorphine delivery system offering ease of use and pharmacokinetic properties suitable as a rescue therapy to treat motor fluctuations (off-episodes) in patients with Parkinson’s disease (PD). This sublingual, thin film strip contains apomorphine, buffer and absorption enhancers which rapidly dissolves when placed under the tongue. APL-130277 quickly produces blood levels in normal volunteers that in patients with PD are known to restore relatively normal motor function and may persist longer than the injectable apomorphine hydrochloride sold under the trade names APO-go, Apokyn, and Apomine for management of “off” episodes in PD.
Disease: Parkinson\'s disease
Therapeutic area: Neurodegenerative diseases
Country: USA
Trial
details: CTH-105 is a Phase 2 clinical study of APL-130277. APL-130277 will be studied in 16 patients with Parkinson\'s disease who are naïve to the use of apomorphine and who experience at least one daily \"off\" episode, with a total duration of \"off\" in any 24-hour period of at least 2 hours. The first patients are expected to enter the screening phase before the end of July. This open-label study will examine the effect of APL-130277 on relieving \"off\" episodes over a single day, with dose-titration used to determine dose strengths necessary for future clinical development. In particular, the dose strength information is necessary in order to conduct the larger CTH-300a efficacy study in apomorphine naïve patients, which is expected to commence in Q4 2014.
Latest
news: * On November 19, 2014, Cynapsus Therapeutics, a specialty pharmaceutical company focused on Parkinson’s disease, announced positive top-line results from its CTH-105 Phase 2 clinical trial of APL-130277 for the management of OFF motor symptoms of Parkinson’s disease. Highlights of the CTH-105 study results include: Out of 16 patients treated with APL-130277, 14 converted from OFF to ON, suggesting that APL-130277 may effectively manage OFF episodes in patients with Parkinson’s disease. Preliminary data show that several subjects converted to ON with the 10mg low dose, and 14 of 16 subjects converted ON with all available doses (i.e. 10, 15, 20, 25 and 30mg). Clinically meaningful improvement in motor control occurred in as early as 10 minutes after administration of APL-130277 and lasted longer than 90 minutes. All five doses of APL-130277 used in the study (10, 15, 20, 25 and 30mg) resulted in patients moving from OFF to ON. The mean baseline UPDRS part III in an OFF state was 41.4, and the maximum mean change from baseline UPDRS part III was 18.4. The mean dose required to convert patients to ON was 18.4mg. The onset of a clinically meaningful improvement was seen in as early as 10 minutes and lasted up to 90 minutes, the last time point measured in this study. The mean time to ON as reported by study staff was 22 minutes. Cynapsus believes that these data strongly support the conclusion that APL-130277 is associated with the robust and rapid management of OFF episodes. The graph shows the mean change from baseline in UPDRS part III for the 14 subjects who converted to ON. Two patients dosed at the highest available dose (30mg) did not achieve a full ON as assessed by the investigator, suggesting that higher doses may be required for some patients. Treatment with APL-130277 was safe and well tolerated. Nausea was reported by three subjects at doses of 10, 15 and 20mg. One of these patients also experienced a mild episode of emesis. There were no reports of nausea at higher doses. There were no reports of local irritation or hypotension in any subject treated. A total of 60 doses of APL-130277 were administered to the 16 patients who completed dosing in the CTH-105 study. Based on the findings of this study, Cynapsus is planning to conduct pivotal studies of longer duration and with larger patient numbers to confirm these results. These pivotal studies are expected to form the registration package necessary for a 505(b)(2) New Drug Application with the FDA expected to be submitted in 2016. * On July 17, 2014, Cynapsus Therapeutics, a specialty pharmaceutical company focused on Parkinson\'s disease, announced that following communication from the FDA on July 16, 2014, Phase 2 clinical studies for APL-130277 will commence immediately. Specifically, clinical study CTH-105 will be initiated per the proposal submitted to the FDA under the Company´s Investigational New Drug (IND) application. APL-130277 is an easy-to-administer, fast-acting reformulation of apomorphine, which is the only approved drug in the United States, Europe, Japan and other countries, to rescue patients from \"off\" episodes experienced with Parkinson\'s disease. APL-130277 will be studied in 16 patients with Parkinson\'s disease who are naïve to the use of apomorphine and who experience at least one daily \"off\" episode, with a total duration of \"off\" in any 24-hour period of at least 2 hours. The first patients are expected to enter the screening phase before the end of July. This open-label study will examine the effect of APL-130277 on relieving \"off\" episodes over a single day, with dose-titration used to determine dose strengths necessary for future clinical development. In particular, the dose strength information is necessary in order to conduct the larger CTH-300a efficacy study in apomorphine naïve patients, which is expected to commence in Q4 2014.
The maximum mean change from baseline UPDRS III was 18.4, which is a large clinically important difference APL-130277 treatment was safe and well tolerated, with no local irritation, no postural hypotension and a low number of nausea events.
