Apomorphine oral spray safe, efficient in Parkinson’s, study finds

Formula promises ‘easier and more user-friendly’ experience

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by Andrea Lobo |

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An oral spray was safe and efficient at delivering apomorphine to people with Parkinson’s disease, a study found.

A subcutaneous injection formulation of apomorphine, sold as Apokyn, is approved in the U.S. to treat off episodes — periods in which symptoms return between doses of levodopa treatment — in people with advanced disease.

The spray formulation “will be an easier and more user-friendly way to administer apomorphine than the recently discontinued sublingual film and currently available subcutaneous injections,” the researchers wrote.

Their study, “Clinical trial evaluating apomorphine oromucosal solution in Parkinson’s disease patients,” was published in Clinical and Translational Science.

Parkinson’s disease is caused by the progressive loss of nerve cells that produce the neurotransmitter dopamine, a brain signaling molecule essential to control muscle movement. Standard treatment includes levodopa and its derivatives, which intend to increase dopamine levels in the brain. However, the long-term use of these treatments can lead to off episodes and dyskinesia, or uncontrolled, involuntary movements.

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Parkinson’s, dexterity, and apomorphine

While the therapy’s exact mechanism of action is not completely understood, apomorphine is thought to work by increasing the potency of dopamine signaling. Administered as a subcutaneous (under-the-skin) injection, it is designed to improve motor symptom control in patients receiving levodopa-based therapies and experiencing off episodes.

Other apomorphine formulations, such as Kynmobi, administered as a sublingual (under-the-tongue) formulation, have also been approved. Kynmobi was discontinued in the U.S. and Canada due to low use.

Both of these formulations require good dexterity and muscle coordination, which are often impaired in Parkinson’s patients.

To overcome these difficulties, an oral spray of highly concentrated apomorphine formulation, called Aporon, is being developed to allow for self-administration using an easy-to-operate device.

The investigational treatment’s safety, tolerability, and pharmacological properties were tested in a Phase 1/2 clinical trial (2019-003315-60).

The study was conducted in Parkinson’s patients, ages 30 to 85, experiencing off periods.

In part A of the study, 12 patients received 2 mg of Aporon and 2 mg subcutaneous apomorphine, followed by 4 mg and 8 mg of Aporon. In part B, 13 patients received 7 mg of Aporon and 30 mg of sublingual apomorphine, followed by 14 mg of Aporon.

The oral formulation was generally well tolerated at all doses tested. Side effects were in accordance with those observed for other apomorphine formulations, including low blood pressure on standing from a sitting or lying position, fatigue, yawning, and somnolence.

The new formula also resulted in fewer side effects in the mouth and pharynx than the sublingual formulation.

As far as pharmacokinetics, or how a medicine moves into, through, and out of the body, results demonstrated that the subcutaneous formulation reached maximum blood levels faster than the oral spray formulation (19 minutes vs. 32 minutes). However, the times were similar when comparing the oral spray with the sublingual formulation, with both achieving the maximum apomorphine blood levels after 45 minutes.

Although the levels of exposure to apomorphine via the oral spray increased with the administered dose, they were below a dose-proportional effect. That meant patients receiving the 8 mg dose of the oral spray had lower exposure than those who got the 2 mg subcutaneous formulation. However, exposures were similar when comparing the oral spray with the sublingual formulation.

The mean maximum exposure in patients given the oral spray formulation was reached with the 14 mg dose, corresponding to a maximum of 8 nanograms (ng)/mL. This was comparable to exposure reached after 2 mg subcutaneous apomorphine, and approximately half of that of 30 mg sublingual formulation.

The “administration of the novel [oral spray] apomorphine solution evaluated in this two-part clinical study was generally well-tolerated and resulted in clinically relevant [blood] concentrations in [Parkinson’s] patients,” the researchers wrote.