The upcoming phase 2b/3 study of mesdopetam in patients with Parkinson disease is set after the results of previous successful phase 1, phase 2a, and phase 2 studies.
IRLAB announced that the FDA has accepted its investigational new drug application (IND) for mesdopetam (also known as IRL790), which will allow IRLAB to include patients from the United States in its upcoming clinical trial of patients with Parkinson disease (PD).1
The planned randomized, double-blinded, placebo-controlled, phase 2b/3 study will assess mesdopetam in its development for the treatment of levodopa induced dyskinesia (LID) in patients with PD across hospitals in the US and Europe. Investigators will examine increases in daily good ON time as the primary end point of the study across a 3-month study duration.
“We are pleased to receive acceptance of the IND. The FDA clearance of the IND is a quality stamp on the mesdopetam project and validates mesdopetam as a safe and tolerable drug candidate. It also means that we now expand our clinical development operations to the US, an important strategic goal for the company,” said Nicholas Waters, PhD, chief executive officer, IRLAB, in a statement.
IRLAB is expected to start patient recruitment for the study during Q4 of 2020. The study has been developed in collaboration with regulatory and clinical experts and will enroll approximately 140 patients evenly distributed across 4 groups: 3 doses of mesdopetam and 1 placebo group.
Mesdopetam acts by antagonizing the dopamine D3 receptor, thus counteracting the physiological effects of the signal substance dopamine. The dopamine D3 receptor is genetically linked to increased risk of involuntary movements and patients with PD-LIDs have higher amounts of D3 receptors in parts of the brain essential for the control of movements.
Data from the phase 2a study with mesdopetam in patients with PD with LIDs indicated that daily time without troublesome dyskinesias increased dose dependently. The best performing dose was 7.5-mg twice daily with good ON time increasing by 5.6 hours daily, compared with 1 hour (P <.002) in the placebo group.
Patients also reported marked improvements without added side effects, demonstrating mesdopetam’s ability to offer a significant qualitative shift in patients’ everyday life.2
"The treatment effects seen in the previous Phase 2a study exceeds the results for other treatment strategies in troublesome dyskinesias,” Joakim Tedroff, MD, PhD chief medical officer, IRLAB, said in a statement. “When mesdopetam was given in addition to standard Parkinson medication, patients experienced considerably longer periods of good daily motor function without aggravated involuntary movements improving the daily function in these severely affected patients. This is highly relevant since involuntary, levodopa-induced dyskinesia is a major problem In Parkinson's disease today preventing optimal individual treatment.”
The results of the phase 2s study also represented a significant improvement of good ON time for these patients who, prior to treatment, had approximately 6.3 hours of good ON per day. The researchers also noted that higher dosing did not show an additional benefit to the patient.
The strategy of the phase 3 study stems from the results of IRLAB’s successful phase 1, phase 2b, and phase 2 studies with mesdopetam, as well as the commonuse of patient diaries in previous marketing authorizations granted by regulatory authorities for treatments in PD.