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®.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
26
Orally inhaled dry powder levodopa from the Cyclops® dry powder inhaler
Orally inhaled dry powder levodopa from the ARCUS® dry powder inhaler
Bed space for short term stay at Diagnostic & Consultative Centre 'Ascendent' Ltd.
Sofia, Bulgaria
The dose at which comparative bioavailability of levodopa will be reached between Levodopa Cyclops® versus Inbrija®
The primary objective of the present trial is to determine the dose at which comparative bioavailability of levodopa will be reached between Levodopa Cyclops® versus Inbrija® in healthy adult subjects after an oral inhalation of a single dose of 45, 90 and 135 mg levodopa under fasting conditions administered with 50 mg carbidopa one hour prior IMP administration in 3 study periods and after a single dose of 66 mg levodopa delivered dose (2 hard capsules containing 42 mg levodopa each) of Inbrija® administered with carbidopa 50 mg one hour prior to IMP administration in a fourth study period.
Time frame: 5 days
The time to reach a levodopa plasma concentration above 400 ng/mL as a measure for the onset of action.
In the scientific literature it is stated that levodopa is effective at plasma concentrations above 400 ng/mL, therefore, the time it takes to reach this concentration with Levodopa Cyclops® and Inbrija® is of interest and is indicative for the onset of action.
Time frame: 5 days
The time above a levodopa plasma concentration 400 ng/mL as a measure for the duration of effect.
In the scientific literature it is stated that levodopa is effective at plasma concentrations above 400 ng/mL, therefore, the time above this concentration after a Levodopa Cyclops® dose or Inbrija® dose is of interest.
Time frame: 5 days
Safety and tolerability of Levodopa Cyclops® by measuring vital signs, laboratory examination and adverse events questioning
Before and after the study: * Vital signs (body temperature, pulse rate, respiratory rate, blood pressure) * 12-lead ECG * Laboratory examination blood and urine (Hematology, Chemistry, Serology, Serum FSH in females, Urinalysis) After each dose: * Adverse event questioning * Vital signs (pulse rate and blood pressure) measurement at 50 minutes post-dose
Time frame: 5 days
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