June 10, 2011 (Toronto, Ontario) — A relatively easy to use and long-lasting inhaled medication is proving to be superior to placebo in reducing "off" periods in patients with Parkinson's disease (PD), according to results of a new study released during the Movement Disorder Society 15th International Congress of Parkinson's Disease and Movement Disorders.

Inhaled apomorphine is less invasive than the injected preparation and has potential benefits for patients with PD, who may find it difficult to administer apomorphine with a needle, said lead author, Donald Grosset, MD, a consultant neurologist at the Institute of Neurological Sciences, Glasgow, Scotland.

Dr. Donald Grosset

He called the study results "encouraging."

Ascending Doses

Patients in the double-blind trial were randomly assigned (on a 3 to 1, active to placebo, basis) to receive a premeasured dry-powder formulation of apomorphine delivered by an inhaler, or a similar placebo.

The study tested 4 ascending doses of the medication — 1.5, 2.5, 3.5, and 4.5 mg — under supervision in a clinic to determine responsiveness. "We started with the lowest dose and moved up if necessary," said Dr. Grosset. Patients then administered their most efficacious dose at home for 4 weeks to abort "off" episodes.

Patients completed diaries twice, for 3 consecutive days.

Two of the 57 patients who were screened dropped out of the study, leaving 55 who were included in the intent-to-treat analysis. Mean age of the patients was 65.6 years, and mean disease duration was 12 years.

The study showed that the Unified Parkinson's Disease Rating Scale 3 (UPDRS 3) improvement in the clinic setting was significantly greater for patients taking apomorphine (19.5 points) than for those taking placebo (9.9 points), which translated into an 8.4-point difference in favor of the inhaled agent (95% confidence interval, 1.2 - 15.5 points; P = .023).

During the at-home phase, 82% of "off" episodes were aborted with apomorphine compared with 13% with placebo, said Dr. Grosset. As well, "off" times were reduced by a longer period in the active group than in the placebo group.

While at home, patients in the active group used the drug 2 to 3 times per day, while use of the puffer by those in the placebo group tended to "drop off" because of lack of efficacy, said Dr. Grosset.

Adverse Events

During the at-home phase, 35% of the apomorphine group and 20% of the placebo group reported adverse events. There were no problems with lung function or systemic irritation, said Dr. Grosset.

As for blood pressure, the response was mixed: Some patients experienced an elevation in blood pressure whereas others had a drop, but none of these changes were "dramatic," he said.

Although response was better with a higher dose of the active drug, higher doses also had more side effects. "Pushing up the dose" may mean entering a "danger zone of side effects," commented Dr. Grosset.

The active medication starts working within about 4 or 5 minutes, with some patients experiencing a response in as little as 1 minute, said Dr. Grosset. Patients found the inhaler easy to use, although it does require "some degree of coordination," he said.

Great Promise

Asked to comment, Janis Miyasaki, MD, associate clinical director of Toronto Western Hospital Movement Disorder Center, said the study findings are "certainly interesting" and "show great promise." The 1-minute onset of the inhaled medication "is quite remarkable" and could offer significant benefits over subcutaneous injections for patients with PD, she said.

Dr. Janis Miyasaki

"If you’re a typical Parkinson patient, you usually have to wait 30 minutes to an hour for your medications to start working, and in advanced cases, dose failures are very common, so you may not get any benefit at all from the dose," she noted.

Some patients with PD have an aversion to needles and also may have difficulty physically giving themselves injections. "If you're a patient with Parkinson's and you’re 'off' and therefore you need the drug, you may not have the manual dexterity to manage a needle," said Dr. Miyasaki.

Also significant is that the drug's duration of action lasted 44 minutes, she added.

Movement Disorders Society (MDS) 15th International Congress of Parkinson's Disease and Movement Disorders: Abstract 385. Presented June 9, 2011.

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