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Safety in Lactation: Dopaminergic drugs used in Parkinsons disease

25 September 2020Although rare, Parkinson’s disease can occur in younger women of childbearing age. Dopamine receptor agonists are used either alone or as an adjunct to levodopa…
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Lactation Safety Information

No
Levodopa, (as co-beneldopa or co-careldopa)
May interfere with lactation
No published evidence of safety
Dopamine receptor agonist
24 September 2020

New Medicines

KynmobiParkinson's disease - treatment of OFF episodes in levodopa responsive patients - sublingual film formulation

Information

Kynmobi
New formulation
BIAL Pharma
Sunovion

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Launched
Sep 21Bial plans to file in the EU before end of 2021 [23].
Sep 21Sunovion Pharmaceuticals enters into a licensing agreement with BIAL. Under the terms of the agreement, BIAL will be responsible for submitting marketing applications in Europe and has exclusive commercial rights for distribution and commercialisation of apomorphine sublingual film in the EU and UK [22].
Dec 20Sunovion Pharmaceuticals Europe is planning to bring apomorphine sublingual film to the UK [20].
Nov 20No plans for EU development in latest DS Pharma annual report or on Sunovion Europe pipeline. Plans for EU/UK development unclear [18,19].
Oct 20Sunovion Pharmaceuticals launches apomorphine sublingual film (Kymobi) in the US for the acute, intermittent treatment of OFF episodes in patients with Parkinsons disease [17].
May 20The US FDA has approved KYNMOBI™ (apomorphine HCI) sublingual film (APL-130277) for the acute intermittent treatment of OFF episodes in patients with Parkinson’s disease [16].
Nov 19Sumitomo Dainippon Pharma reconfirms its intention to resubmit an NDA for OFF episodes associated with Parkinson’s disease in the US; nil re EU plans [14].
Nov 19Has fast track status in US for the treatment of PD [13].
Apr 19Sumitomo Dainippon Pharma and Sunovion Pharmaceuticals announce their intention to re-submit a NDA to the US FDA in 2019 [12].
Jan 19In a Complete response letter, the FDA has rejected APL-130277, and requested additional information and analyses [11].
Mar 18Filed in the US to treat motor fluctuations (OFF episodes) experienced by people living with PD [9].
Jan 17Sunovion plans to file in the US during Q2-3 17, following completion of CTH-200, CTH-300 and CTH-301 studies [7].
Aug 16Sunovion has bought out Cynapsus [5].
Mar 15Cynapsus Therapeutics plans to file in the US in 2016 [3]

Category

Dopamine receptor agonist (fast-acting, sublingual, thin filmstrip formulation of apomorphine)
PD is the second most common neurodegenerative disorder after Alzheimers disease. It typically develops between the ages of 55 and 65 years and occurs in 1-2% of people over the age of 60 years, rising to 3.5% at age 85-89 years. About 0.3% of the general population is affected, and the prevalence is higher among men than women, with a ratio of 1.5 to 1 [24].
Parkinson's disease - treatment of OFF episodes in levodopa responsive patients - sublingual film formulation
Sublingual

Trial or other data

Apr 22PIII CTH-301 (NCT02542696) has finished recruiting [25].
Dec 20PIII CTH-301 (NCT02542696) is recruiting and collection of primary outcome data is now due to complete Jul 22 [21].
Dec 19PIII RCT (NCT02469090; n=109) is published in the Lancet. It reports improvement in “off episodes” with mean change from pre-dose to 30min post-dose in MDS-UPDRS score at week 12 (primary endpoint) greater for patients who received sublingual apomorphine v those receiving placebo (−11.1 v −3.5 respectively (p=0.0002) [14].
Nov 18PIII CTH-300 study (NCT02469090) is complete [10].
Mar 18PIII CTH-301 (NCT02542696) is still recruiting & collection of primary outcome data is now due to complete Jan 20 [10].
Aug 17PIII development is still continuing. PIII CTH-300 study (NCT02469090) has completed recruitment, and is due to complete collection of primary outcome data in Nov 17. PIII CTH-301 (NCT02542696) is still recruiting & collection of primary outcome data is due to complete Mar 18 [8].
Jan 17Both PIII studies expected to complete in Mar 17 [5].
Jan 16Two US PIII studies are ongoing. NCT02469090 is a 12-week double-blind RCT of APL-130277 in 126 levodopa-responsive patients with Parkinson´s Disease complicated by motor fluctuations (‘off’ episodes). The study started in Jun 15 and is due to complete in Apr 16. NCT02542696 is a 24-week open-label longer-term safety study in 226 PD patients responsive to levodopa, which is due to complete Nov 16 [4].
Mar 15Comany announces plans for PIII Pivotal Program to evaluate the safety and efficacy of APL-130277 for PD patients. The CTH-200 bridging study, CTH-300 efficacy study and CTF-301 safety studies will begin in the second quarter of 2015 with a view to submitting a New Drug Application (NDA) in 2016 [2].
Nov 14Cynapsus Therapeutics (CYNAF) announced positive top-line results from its PII multicentre open-label study (CTH-105) of APL-130277 for the management of OFF motor symptoms of PD. APL-130277 was assessed in 16 pts with PD who experienced debilitating OFF episodes for at least 2 hours daily. Debilitating OFF episodes were induced by not allowing pts to take their morning dose of levodopa. Pts were then given escalating doses of APL-130277 (10, 15, 20, 25 and 30mg) with at least 3 between doses until ON was achieved. Staff and pts were involved in assessment of symptoms using the Unified Parkinson’s Disease Rating Scale (UPDRS) part III scale at 15, 30, 45, 60 and 90 minutes. This scale is used by neurologists to measure severity of PD OFF and motor symptoms, compared with baseline. Fourteen of 16 pts treated with APL-130277 converted from OFF to ON at all available doses (i.e. 10, 15, 20, 25 and 30mg). The mean dose needed to terminate the OFF episode was 18.4mg. Clinically meaningful improvement in motor control occurred as early as 10 minutes after dosing and lasted longer than 90 minutes. The maximum mean change from a baseline UPDRS III was 18.4 (a 45% improvement from baseline), which is considered to be a 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 (3/16 experienced nausea each at 10mg, 15mg and 20mg). Larger pivotal PIII studies are planned to take place over a longer duration to confirm these results and a New Drug Application (NDA) is expected to be submitted in 2016 [1].

Evidence based evaluations