Apomorphine Reduces Off Time for People with Advanced Parkinson’s Disease

BOSTON—Apomorphine may provide relief from off time for people with advanced Parkinson’s disease, according to a study presented at the 69th Annual Meeting of the American Academy of Neurology.

“If a person with Parkinson’s disease can reduce their off times, that can have a great impact on their everyday life,” said study author Regina Katzenschlager, MD, of Danube Hospital, which is affiliated with the Medical University of Vienna. “In some patients in the trial, the insecurity of unpredictable periods of incapacity was completely alleviated.”

Open-Label Data Suggest Efficacy

Levodopa has long been the gold standard in the treatment of Parkinson’s disease, but the effects of the medication can partially wear off more quickly as the disease progresses. Patients consequently experience off time that includes symptoms such as slowness and muscle rigidity.

The drug apomorphine, which first was produced in 1865, began to be used to treat advanced Parkinson’s disease in the United States in 1950. Its use grew in the 1990s when European doctors started administering subcutaneous infusions of the drug to treat fluctuations in mobility that could not be controlled by levodopa.

Extensive data from open-label studies of apomorphine have demonstrated its efficacy in reducing off time, dyskinesias, and oral levodopa dose in patients with severe motor fluctuations that are poorly controlled by conventional therapy. Evidence from randomized, blinded studies of the drug has been lacking, however.

Comparing Apomorphine With Placebo

In a double-blind phase III study, researchers recruited 107 people with advanced Parkinson’s disease from 23 centers in seven countries.

Participants were randomized to either apomorphine subcutaneous infusion (≤ 8 mg/h) or a placebo saline infusion. The infusion was administered over a period of 14 to 18 hours each day through a small portable pump similar to the type used in the treatment of type 1 diabetes. The hourly flow rate of the infusion and dose of concomitant antiparkinsonian medication were adjusted during the first four weeks, based on efficacy and tolerability. The study’s primary end point was the absolute change in off time from baseline to Week 12 based on patient diaries.

Patients who received apomorphine had a significantly greater reduction of off time than those who received the placebo infusion. Active patients had, on average, 2.5 hours less off time per day, while participants who received the placebo infusion had an average of 35 minutes less off time per day. This improvement was apparent within the first week of treatment and was sustained over 12 weeks. At the same time, patients who received apomorphine had a significantly greater increase of on time without the dyskinesias that often are observed with levodopa, compared with placebo.

Participants were also asked to evaluate how well they thought the treatment worked. Those who received apomorphine gave their treatment higher scores at week 12 than those who received the placebo infusion. In the apomorphine group, 71% of patients felt improved, compared with 18% of patients who received placebo. Furthermore, 19% of patients worsened on apomorphine, compared with 45% on placebo. Apomorphine was generally well tolerated, and the researchers observed no serious side effects.

“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,” Dr. Katzenschlager
concluded.

The study was supported by Britannia Pharmaceuticals, the maker of apomorphine.

BOSTON—Apomorphine may provide relief from off time for people with advanced Parkinson’s disease, according to a study presented at the 69th Annual Meeting of the American Academy of Neurology.

“If a person with Parkinson’s disease can reduce their off times, that can have a great impact on their everyday life,” said study author Regina Katzenschlager, MD, of Danube Hospital, which is affiliated with the Medical University of Vienna. “In some patients in the trial, the insecurity of unpredictable periods of incapacity was completely alleviated.”

Open-Label Data Suggest Efficacy

Levodopa has long been the gold standard in the treatment of Parkinson’s disease, but the effects of the medication can partially wear off more quickly as the disease progresses. Patients consequently experience off time that includes symptoms such as slowness and muscle rigidity.

The drug apomorphine, which first was produced in 1865, began to be used to treat advanced Parkinson’s disease in the United States in 1950. Its use grew in the 1990s when European doctors started administering subcutaneous infusions of the drug to treat fluctuations in mobility that could not be controlled by levodopa.

Extensive data from open-label studies of apomorphine have demonstrated its efficacy in reducing off time, dyskinesias, and oral levodopa dose in patients with severe motor fluctuations that are poorly controlled by conventional therapy. Evidence from randomized, blinded studies of the drug has been lacking, however.

Comparing Apomorphine With Placebo

In a double-blind phase III study, researchers recruited 107 people with advanced Parkinson’s disease from 23 centers in seven countries.

Participants were randomized to either apomorphine subcutaneous infusion (≤ 8 mg/h) or a placebo saline infusion. The infusion was administered over a period of 14 to 18 hours each day through a small portable pump similar to the type used in the treatment of type 1 diabetes. The hourly flow rate of the infusion and dose of concomitant antiparkinsonian medication were adjusted during the first four weeks, based on efficacy and tolerability. The study’s primary end point was the absolute change in off time from baseline to Week 12 based on patient diaries.

Patients who received apomorphine had a significantly greater reduction of off time than those who received the placebo infusion. Active patients had, on average, 2.5 hours less off time per day, while participants who received the placebo infusion had an average of 35 minutes less off time per day. This improvement was apparent within the first week of treatment and was sustained over 12 weeks. At the same time, patients who received apomorphine had a significantly greater increase of on time without the dyskinesias that often are observed with levodopa, compared with placebo.

Participants were also asked to evaluate how well they thought the treatment worked. Those who received apomorphine gave their treatment higher scores at week 12 than those who received the placebo infusion. In the apomorphine group, 71% of patients felt improved, compared with 18% of patients who received placebo. Furthermore, 19% of patients worsened on apomorphine, compared with 45% on placebo. Apomorphine was generally well tolerated, and the researchers observed no serious side effects.

“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,” Dr. Katzenschlager
concluded.

The study was supported by Britannia Pharmaceuticals, the maker of apomorphine.

BOSTON—Apomorphine may provide relief from off time for people with advanced Parkinson’s disease, according to a study presented at the 69th Annual Meeting of the American Academy of Neurology.

“If a person with Parkinson’s disease can reduce their off times, that can have a great impact on their everyday life,” said study author Regina Katzenschlager, MD, of Danube Hospital, which is affiliated with the Medical University of Vienna. “In some patients in the trial, the insecurity of unpredictable periods of incapacity was completely alleviated.”

Open-Label Data Suggest Efficacy

Levodopa has long been the gold standard in the treatment of Parkinson’s disease, but the effects of the medication can partially wear off more quickly as the disease progresses. Patients consequently experience off time that includes symptoms such as slowness and muscle rigidity.

The drug apomorphine, which first was produced in 1865, began to be used to treat advanced Parkinson’s disease in the United States in 1950. Its use grew in the 1990s when European doctors started administering subcutaneous infusions of the drug to treat fluctuations in mobility that could not be controlled by levodopa.

Extensive data from open-label studies of apomorphine have demonstrated its efficacy in reducing off time, dyskinesias, and oral levodopa dose in patients with severe motor fluctuations that are poorly controlled by conventional therapy. Evidence from randomized, blinded studies of the drug has been lacking, however.

Comparing Apomorphine With Placebo

In a double-blind phase III study, researchers recruited 107 people with advanced Parkinson’s disease from 23 centers in seven countries.

Participants were randomized to either apomorphine subcutaneous infusion (≤ 8 mg/h) or a placebo saline infusion. The infusion was administered over a period of 14 to 18 hours each day through a small portable pump similar to the type used in the treatment of type 1 diabetes. The hourly flow rate of the infusion and dose of concomitant antiparkinsonian medication were adjusted during the first four weeks, based on efficacy and tolerability. The study’s primary end point was the absolute change in off time from baseline to Week 12 based on patient diaries.

Patients who received apomorphine had a significantly greater reduction of off time than those who received the placebo infusion. Active patients had, on average, 2.5 hours less off time per day, while participants who received the placebo infusion had an average of 35 minutes less off time per day. This improvement was apparent within the first week of treatment and was sustained over 12 weeks. At the same time, patients who received apomorphine had a significantly greater increase of on time without the dyskinesias that often are observed with levodopa, compared with placebo.

Participants were also asked to evaluate how well they thought the treatment worked. Those who received apomorphine gave their treatment higher scores at week 12 than those who received the placebo infusion. In the apomorphine group, 71% of patients felt improved, compared with 18% of patients who received placebo. Furthermore, 19% of patients worsened on apomorphine, compared with 45% on placebo. Apomorphine was generally well tolerated, and the researchers observed no serious side effects.

“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,” Dr. Katzenschlager
concluded.

The study was supported by Britannia Pharmaceuticals, the maker of apomorphine.