NeuroDerm’s Phase 2 Parkinson’s disease (PD) trial of ND0612H — a continuous infusion of levodopa and carbidopa delivered by a small belt pump — has met both primary and key secondary endpoints by demonstrating that the treatment effectively reduced “off-time” and increased the number of patients with advanced Parkinson’s who experienced treatment effects in the morning.
In fact, nearly two-thirds of those who responded to the treatment in the trial, referred to as trial 006 by the company, had no off-time at all. Off-time is the time when the effects of Parkinson’s drugs wears off.
“The very prominent responder effect, as well as the significant reductions in OFF-time and troublesome dyskinesia [voluntary movement impairment] observed in trial 006, are extremely encouraging and demonstrate the substantial potential for ND0612 to make a meaningful difference in the lives of patients living with Parkinson’s disease,” NeuroDerm CEO Oded S. Lieberman, PhD, said in a press release.
The trial (NCT02577523) enrolled 38 participants across the E.U., Israel, and the U.S., who were randomized to receive either 24 or 14 hours of the infusion. The first group, called R1, received ND0612H 720 mg of levodopa and 90 mg of carbidopa at a high day rate for 18 hours and a low nighttime rate for six hours.
The second group, R2, was treated with 538 mg of levodopa and 68 mg carbidopa during 14 hours in the day, and an additional morning dose of 150 mg and 15 mg of the two drugs.
Both groups were treated for 28 days, and the patients could add oral levodopa and carbidopa treatment as needed throughout the day.
The R1 group, which had an average off-time of 5.5 hours per day, reduced the time without drug benefits by 2.8 hours — a statistically significant difference that allowed the study to meet its primary endpoint. Those in the R2 group also experienced less off-time, but the decrease by 1.3 hours was not significant.
Since patients usually experience off-time in the morning, the study also measured how many patients experienced symptoms at 8 a.m. and 9 a.m.
Among those receiving the 24-hour infusion, on-time at 8 a.m. increased from 11 percent to 50 percent after 28 days. At 9 a.m., 75 percent of the patients had symptom relief.
Since the R2 group’s dosing began in the morning, there was no improvement in morning symptom relief in these patients.
The trial also assessed what researchers called “good on-time.” By this, they meant symptom relief with no or mild dyskinesia. In the R1 group, participants had a daily average of 9.2 hours of good on-time. This increased to 12.9 hours. The R2 group increased good on-time from 8.5 hours to 11.3 hours.
In addition, oral dosing, troublesome dyskinesias, and symptom severity were reduced by the treatment in both groups.
Five patients stopped the treatment early, two of whom had adverse effects. One patient had an infection at the infusion site, while the other patient had worsening symptoms. Infusion-site reactions were common, but were most often well-tolerated. In contrast, patients did not report any inconvenience from wearing the pump device, either during the day or at night.
The company also announced that it has modified its clinical and regulatory development strategy within the E.U. after a meeting with the European Medicines Agency (EMA).
The new strategy means that the previously planned pharmacokinetic trial will not be carried out. Pharmacokinetics is the study of how a drug is processed in the body, including its distribution, metabolism, and excretion.
Instead, results from the re-started and amended Phase 3 iNDiGO trial (NCT02782481) and the ongoing BeyoND (NCT02726386) long-term safety trial will be used to submit a marketing application for ND0612H. In this way, NeuroDerm hopes to obtain a broader label for ND0612H than the one that would have been granted using pharmacokinetics data.
The altered strategy will not impact the timelines for the E.U. marketing application submission or the clinical and regulatory development schedule in the U.S.