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BOSTON -- In patients with Parkinson's Disease (PD), apomorphine subcutaneous infusion (APO) provided hours of daily relief from the sudden and unpredictable fluctuations in motor function know as "Off" time, researchers said.

Results from the phase III Toledo trial demonstrated that in 107 patients randomized to either subcutaneous APO infusion or placebo, those who received active treatment experienced an average of 2.47 hours less "Off" time each day without dyskinesias compared with an average of 0.58 fewer "Off" hours each day for those given placebo, according to Regina Katzenschlager, MD, of the Medical University of Vienna, and colleagues.

The difference between the treatment groups was 1.89 hours (P=0.0025), according to the authors, who will present their results here at the American Academy of Neurology annual meeting next week.

Treatment was also associated with a significant increase in mobility or "On" time, producing higher scores on scale versus placebo (P<0.001).

Additionally, the regimen was generally well tolerated with no unexpected adverse events, the authors stated.

"These results show level 1 evidence that APO provides a significant and clinically meaningful reduction in OFF time without increasing dyskinesias in patients whose motor fluctuations cannot be controlled with current standard of care, filling an important knowledge gap," Katzenschlager's group stated.

Motor complications, including an impaired ability to move, muscle stiffness, and tremor, occur in at least 50% of Parkinson's disease patients who have received levodopa for 5-10 years and constitute a major cause of disability in advanced disease. After 50 years of clinical experience, oral levodopa, coupled with carbidopa, remains the gold standard of symptomatic treatment for Parkinson's disease, despite the motor complications associated with its long-term use.

Extensive data from open-label studies with APO have demonstrated its efficacy in reducing "Off" time with conventional oral levodopa therapy, Katzenschlager pointed out. Until now, however, evidence from randomized, blinded studies has been lacking.

APO infusion is used in Europe, but has not been approved for use in this patient population in the U.S.

For the prospective, double-blind study, patients with advanced Parkinson's disease were recruited from 23 centers in seven countries. They were randomized to either APO subcutaneous infusion or a placebo saline infusion over a period of 14-18 hours from identical portable pumps.

When patients were asked to evaluate treatment, 71% of patients in the APO group said they felt better compared with 18% receiving placebo. Conversely, 45% of patients in the placebo group said they felt worse after treatment compared with 19% in the APO group.

"It is our hope that these findings confirming the efficacy of apomorphine infusion will encourage doctors in the United States to offer this treatment to their patients and assess its efficacy in their own clinical practice," said Katzenschlager in a statement.

In addition to clinical benefits, there was a significant impact on quality of life, she noted. "In some patients in the trial, the insecurity of unpredictable periods of incapacity was completely alleviated," she noted.

The Toledo trial could provide the data needed to "allow thousands of American patients to have the chance to benefit from a cheap and effective therapy," study co-author Andrew Lees, MD, of University College London, wrote in an email. The reduction in "Off" time is also much greater than that reported with recently marketed oral drugs such as safinamide (Xadago) and opicapone (Ongentys), he noted.

Although it's an older drug without a patent, APO can restore independence to severely handicapped patients while also improving non-motor symptoms in the "Off" period, including bladder and bowel disturbances and pain, Lees said. The Toledo trial used state-of-the-art clinical trial methodology to confirm what has been known for more than 20 years, he pointed out.

"The Toledo study fills an evidence-based gap for apomorphine in the same way the study did a decade ago for levodopa treatment in Parkinson's Disease," Lees told 番茄社区. "Apomorphine is an efficacious treatment for advanced Parkinson's disease where refractory motor fluctuations are present despite optimum oral and patch anti-Parkinsonian therapy. The FDA needs to grant apomorphine pump therapy a licence for use in the treatment of Parkinson's disease."

Rajesh Pahwa, MD, of the University of Kansas Medical Center in Kansas City, Mo., agreed. "The data can be submitted to the FDA to obtain approval for this therapy," he said in an email.

Pahwa, who was not affiliated with the trial, noted that APO injections are available in the U.S. but only as rescue therapy for short-term control of symptoms. "We need additional therapy to reduce 'Off' time, and this is an additional option," he said.

At present, there are no data to indicate whether APO is superior to currently available therapies such as carbidopa/levodopa enteral suspension therapy (Duopa therapy) or deep brain stimulation, Pahwa pointed out. Duopa was approved by the FDA in early 2015 while in Europe, Duodopa was approved in 2004.)

However, he noted that no adverse effects were reported in the Toledo trial, adding that formation of subcutaneous nodules is one of the main concerns with subcutaneous therapy.

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