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

NCT06037590 | Completed Phase 1

• 1 other identifier: 2023-504687-42-00
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief 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®.

Conditions

Parkinson; Parkinson Disease; Parkinson's Disease and Parkinsonism

Keywords

Cyclops®; Levodopa Cyclops®; Cyclops; Inhaled levodopa; OFF episodes; motor fluctuations

Outcome Measures

Primary Outcomes (1)

• 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.

  5 days

Secondary Outcomes (3)

• The time to reach a levodopa plasma concentration above 400 ng/mL as a measure for the onset of action.

  5 days

• The time above a levodopa plasma concentration 400 ng/mL as a measure for the duration of effect.

  5 days

• Safety and tolerability of Levodopa Cyclops® by measuring vital signs, laboratory examination and adverse events questioning

  5 days

Study Arms (4)

Test 1 - Levodopa Cyclops® 45 mg

EXPERIMENTAL

1 pre-filled single-use Levodopa Cyclops® (= 45 mg levodopa)

Combination Product: Levodopa Cyclops®

Test 2 - Levodopa Cyclops® 90 mg

EXPERIMENTAL

2 pre-filled single-use Levodopa Cyclops® devices (= 90 mg levodopa)

Combination Product: Levodopa Cyclops®

Test 3 - Levodopa Cyclops™ 135 mg

EXPERIMENTAL

3 pre-filled single-use Levodopa Cyclops® devices (= 135 mg levodopa)

Combination Product: Levodopa Cyclops®

Reference - Inbrija® 84 mg

ACTIVE COMPARATOR

2 Inbrija® capsules (42 mg levodopa per capsule) from the Arcus® dry powder inhaler

Combination Product: INBRIJA®

Interventions

Levodopa Cyclops® COMBINATION_PRODUCT

Orally inhaled dry powder levodopa from the Cyclops® dry powder inhaler

Test 1 - Levodopa Cyclops® 45 mg; Test 2 - Levodopa Cyclops® 90 mg; Test 3 - Levodopa Cyclops™ 135 mg

INBRIJA® COMBINATION_PRODUCT

Orally inhaled dry powder levodopa from the ARCUS® dry powder inhaler

Reference - Inbrija® 84 mg

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female subject
• Age between 18 and 55 years (inclusive the date of signing informed consent)
• Female subject who IS NOT of reproductive potential. A female subject who is NOT of reproductive potential is defined as one who:
• (i) has reached natural menopause (defined as at least 6 months of spontaneous amenorrhea with serum follicle-stimulating hormone \[FSH\] levels in the postmenopausal range as determined by the local laboratory, or 12 months of spontaneous amenorrhea); (ii) is 6 weeks post-surgical bilateral oophorectomy with or without hysterectomy; or (iii) has undergone bilateral tubal ligation. Spontaneous amenorrhea does not include cases for which there is an underlying disease that causes amenorrhea (e.g. anorexia nervosa)
• Female subject who IS of reproductive potential and uses reliable contraception method and/or is willing to use adequate birth control methods starting from the time of consent through 30 days after the last dose of study therapy
• List of medically accepted contraceptive methods (used at least 4 weeks prior screening visit and not to be changed for the duration of the study):
• Combination of a barrier method and spermicides (film, jelly, foam): e.g. female/ male condoms with spermicides, as well as diaphragm/ cervical cap/ contraceptive sponge with spermicides.
• Hormonal methods: combined estrogen/progestin injectable and oral contraceptives; progestin injectable and oral contraceptives; implants (Nexplanon®), vaginal ring (NuvaRing®), skin patch (Xulane®) and contraceptive injection (Depo-Provera®).
• Intrauterine devices (IUD): inert or copper IUD (ParaGard®), hormonal IUD (Mirena®, Skyla®, Kyleena®).
• Physically and mentally healthy as judged by means of medical and standard laboratory examination
• Non-smokers or ex-smokers (stopped at least 6 months ago) with a smoking history of ≤5 pack-year equivalents (1 pack-year equivalent is equal to smoking 1 pack per day for 1 year) and non-users of othernicotine containing products, confirmed by urine cotinine test
• BMI within the range (including the borders) of 18.0 to 30.0 kg/m2
• Normal spirometry values at screening (forced expiratory volume in one second \[FEV1\] and forced vital capacity \[FVC\] between 80% and 120% of the average value regarding age, height, gender and ethnicity (acc. to ECCS/ERS)1
• Informed consent given in written form according to chapter 5.4 of clinical trial protocol

You may not qualify if:

• Participation in another clinical trial at same time or within 90 days before screening visit (calculated from the date of the final examination of the previous study)
• Randomization into the present trial more than once
• Pregnant and/or nursing women. Positive pregnancy test
• Weight of less than 40 kg
• Blood donation or blood loss including plasmapheresis of \>500 mL within 90 days before screening visit
• History of drug abuse or use of illegal drugs: use of soft drugs, e.g. marihuana within 6 months before screening visit or hard drugs, e.g. cocaine, amphetamines, phencyclidine within 1 year before screening visit
• Alcohol abuse, i.e. regular use of more than 2 units of alcohol per day or 10 units per week or a history of alcoholism (one unit of alcohol equals 250 mL beer, 125 mL wine or 25 mL spirits) or recovered alcoholics
• Regular consumption of beverages or food containing methylxanthines (e.g. coffee, tea, cola, caffeine containing sodas, chocolate) equivalent to more than 500 mg methylxanthines per day
• Positive drug screening
• Positive alcohol test
• History of significant multiple and/or severe allergies (including latex allergy, asthma or bronchial hyperreactivity), or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food
• Any history of drug hypersensitivity (especially to the active ingredient levodopa of the Test and Reference IMPs and to the active ingredient carbidopa of the AxMP) or intolerance to any sugar (e.g. fructose, glucose, or lactose)
• Presence or a history of clinically significant cardiovascular, renal, hepatic, pulmonary, metabolic, endocrine, hematological, gastrointestinal, neurological, psychiatric or other diseases
• Clinically significant illness within 4 weeks before screening visit
• Major surgery of the gastrointestinal tract except for appendectomy

Sponsors & Collaborators

• PureIMS B.V.: lead
• Cooperative Clinical Drug Research and Development AG (CCDRD AG): collaborator

Study Sites (1)

Bed space for short term stay at Diagnostic & Consultative Centre 'Ascendent' Ltd.

Sofia, 1202, Bulgaria

Location

MeSH Terms

Conditions

Parkinson Disease; Parkinsonian Disorders; cyclopia sequence

Interventions

Dihydroxyphenylalanine

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Catecholamines; Amines; Organic Chemicals; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Tyrosine

Study Officials

• Ivo Bogdanov, MD

  Bed space for short term stay at Diagnostic & Consultative Centre 'Ascendent' Ltd.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open-label, randomized, crossover, comparative bioavailability study in healthy volunteers

Study Record Dates

• First Submitted: August 24, 2023
• First Posted: September 14, 2023
• Study Start: September 25, 2023
• Primary Completion: October 20, 2023
• Study Completion: October 27, 2023
• Last Updated: May 31, 2025

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

BU (1)