NCT06037590

A Pilot Comparative Bioavailability Study of Levodopa Administered Via Levodopa Cyclops® Relative to INBRIJA®

A Pilot Open-label, Randomized, Crossover, Comparative Bioavailability Study of Levodopa Administered Via Levodopa Cyclops® (Test Product) Relative to INBRIJA® (Reference Product) in Healthy Adult Subjects

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 26 (actual)
• Sponsor: PureIMS B.V. · Industry
• Sex: All
• Age: 18 Years – 55 Years
• Healthy volunteers: Accepted

Summary

Patients with Parkinson's disease (PD) are commonly treated with a combination of levodopa and a decarboxylase inhibitor (DCI). However, many PD patients experience motor fluctuations (OFF episodes), even with their regular levodopa/DCI treatment. This unmet medical need was addressed by the approval of INBRIJA®, an orally inhaled product, for producing therapeutic relief during the OFF episodes. INBRIJA® is a capsule-based inhaler system and in order to administer the full dose of levodopa, the patients need to inhale the contents of two capsules. In order to administer the full dose of levodopa, patients need to inhale the contents of two capsules. Since the INBRIJA® device is a standalone and reusable unit, the patients have to load the capsule prior to inhalation several times a day during the OFF episodes (except early-morning OFF) to get relief. Also, the INBRIJA® device is repeatedly used by PD patients and therefore needs to be properly cleaned to avoid contamination. PureIMS is developing a more user-friendly alternative called Levodopa Cyclops®, a pre-filled drug-device combination of levodopa inhalation powder for use with the Cyclops® dry powder inhaler. Due to the nature of the Cyclops®, it offers PD patients greater ease and convenience in use. Moreover, the device's moderate to high resistance to airflow and minimal use of excipients suggests minimal cough episodes during oral inhalation. The current study is planned in order to determine the dose at which comparative bioavailability of Levodopa Cyclops® will be reached compared to INBRIJA®.

Detailed description

Patients with Parkinson's disease (PD) are commonly treated with a combination of levodopa and a decarboxylase inhibitor (DCI). However, many PD patients experience motor fluctuations (OFF episodes), even with their regular levodopa/DCI treatment. This unmet medical need was addressed by the approval of INBRIJA®, an orally inhaled product, which releases levodopa in the systemic circulation for producing therapeutic relief during the OFF episodes. The INBRIJA® inhaler system is based on a spray-dried powder and contains 90% of levodopa, 8% dipalmitoyl phosphatidylcholine, and 2% sodium chloride. In order to administer the full dose of levodopa, patients need to inhale the contents of two capsules. Since the INBRIJA® device is a standalone and reusable unit, the patients have to load the capsule prior to inhalation several times a day during the OFF episodes (except early-morning OFF) to get relief. Also, the INBRIJA® device is repeatedly used by PD patients and therefore needs to be properly cleaned to avoid contamination. PureIMS is developing a drug-device combination product called Levodopa Cyclops®, a pre-filled drug-device combination of levodopa inhalation powder for use with the Cyclops® dry powder inhaler. The ready-to-use Cyclops® carries a high load of drug (i.e., 98% levodopa with only 2% L-leucine serving as the excipient). Due to the nature of the Cyclops®, it offers PD patients greater ease and convenience in use. Moreover, the device's moderate to high resistance to airflow and minimal use of excipients suggests minimal cough episodes during oral inhalation. Levodopa Cyclops® has shown safety and tolerability in PD patients with no reports of cough episodes. The pharmacokinetics (PK) at 30, 60 and 90 mg Levodopa Cyclops® doses show a dose proportional increase of exposure (Cmax and AUC) with a rapid attainment of Cmax (within 10 minutes after oral inhalation using Levodopa Cyclops®). PureIMS plans to pursue drug development in the US via the 505(b)(2) regulatory pathway, referencing the safety and efficacy findings of the FDA for the approved levodopa inhaler INBRIJA®. The current study is planned in order to determine the dose at which comparable relative bioavailability of Levodopa Cyclops® will be reached compared to INBRIJA®. The selected Levodopa Cyclops® dose will then be investigated against INBRIJA® in a formal comparative bioavailability study, in order to provide a PK bridge of Levodopa Cyclops® to the reference listed drug.

Conditions

• Parkinson
• Parkinson Disease
• Parkinson's Disease and Parkinsonism

Interventions

Type	Name	Description
COMBINATION_PRODUCT	Levodopa Cyclops®	Orally inhaled dry powder levodopa from the Cyclops® dry powder inhaler
COMBINATION_PRODUCT	INBRIJA®	Orally inhaled dry powder levodopa from the ARCUS® dry powder inhaler

Timeline

• Start date: 2023-09-25
• Primary completion: 2023-10-20
• Completion: 2023-10-27
• First posted: 2023-09-14
• Last updated: 2025-05-31

Locations

1 site across 1 country: Bulgaria