A Pilot Comparative Bioavailability Study of Levodopa Administered Via Levodopa Cyclops™ Relative to INBRIJA®
Condition: Parkinson; Parkinson Disease; Parkinson's Disease and Parkinsonism
MeSH terms: Parkinson Disease; Parkinsonian Disorders
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): Levodopa Cyclops™; INBRIJA®
Intervention type(s): Combination Product; Combination Product
Intervention description(s): Orally inhaled dry powder levodopa from the Cyclops™ dry powder inhaler; Orally inhaled dry powder levodopa from the ARCUS® dry powder inhaler
Intervention MeSH terms: Levodopa
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Open-label, randomized, crossover, comparative bioavailability study in healthy volunteers
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Cyclops™; Levodopa Cyclops™; Cyclops; Inhaled levodopa; OFF episodes; motor fluctuations