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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

CCDRD Cooperative Clinical Drug Research and Development AG, PureIMS B.V.

Participant type

Healthy volunteers

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

19 Sep 2023 → 9 Nov 2023

Decision date (initial)

2023-08-15

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

PureIMS B.V. Ceintuurbaan Noord 152 9301 NZ Roden The Netherlands

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic

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.

Secondary objectives 3

1. 1. To determine the comparative time to reach a levodopa plasma concentration above 400 ng/mL via Levodopa Cyclops™ versus Inbrija®.
2. 2. To determine the comparative time above a levodopa plasma concentration 400 ng/mL via Levodopa Cyclops™ versus Inbrija®.
3. 3. To determine the safety and tolerability of Levodopa Cyclops™ in healthy adult subjects.

Conditions and MedDRA coding

No therapeutic indication in the current trial with healthy volunteers. The intended indication is for intermittent treatment of episodic motor fluctuations (OFF episodes) in adult patients with Parkinson’s disease (PD) treated with a levodopa/dopa-decarboxylase inhibitor.

Study design 4 periods

Regulatory references

Scientific advice from competent authorities

Medicines Evaluation Board, Food And Drug Administration

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. [1] Male or female subject
2. [2] Age between 18 and 55 years (inclusive the date of signing informed consent)
3. [3] 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)
4. [4] 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
5. [5] Physically and mentally healthy as judged by means of medical and standard laboratory examination
6. [6] 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 other nicotine containing products, confirmed by urine cotinine test
7. [7] BMI within the range (including the borders) of 18.0 to 30.0 kg/m2
8. [8] 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)
9. [9] Informed consent given in written form according to chapter 5.4 of clinical trial protocol

Exclusion criteria 30

1. [1] 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)
2. [2] Randomization into the present trial more than once
3. [3] Pregnant and/or nursing women. Positive pregnancy test
4. [4] Weight of less than 40 kg
5. [5] Blood donation or blood loss including plasmapheresis of >500 mL within 90 days before screening visit
6. [6] 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
7. [7] 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
8. [8] 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
9. [9] Positive drug screening
10. [10] Positive alcohol test
11. [11] 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
12. [12] 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)
13. [13] Presence or a history of clinically significant cardiovascular, renal, hepatic, pulmonary, metabolic, endocrine, hematological, gastrointestinal, neurological, psychiatric or other diseases
14. [14] Clinically significant illness within 4 weeks before screening visit
15. [15] Major surgery of the gastrointestinal tract except for appendectomy
16. [16] Any chronic disease which might interfere with resorption, distribution, metabolism or excretion of the drug
17. [17] History of difficulty in swallowing
18. [18] Positive serologic findings for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HBsAg), and/or hepatitis C virus (HCV) antibodies
19. [19] Administration of depot injectable solutions or medications with a half-life >1 week (including study medications) within 6 months before screening visit
20. [20] Intake of enzyme-inducing, organotoxic or long half-life drugs within 4 weeks before screening visit
21. [21] Intake or administration of any systemic or topical medication (including OTC medication and especially intake of antacids e.g. aluminum hydroxide, magnesium hydroxide, and simethicone or herbal medication e.g. St. John's wort, kava kava) within 2 weeks before screening visit
22. [22] Medication with drugs known to alter the major organs or systems such as barbiturates, phenothiazines, cimetidine, omeprazole etc. within 60 days before screening visit
23. [23] Systolic blood pressure outside the range of 100 to 135 mmHg and/or diastolic blood pressure outside the range of 60 to 90 mmHg
24. [24] Pulse rate outside the range of 50 to 90 beats/min
25. [25] Respiratory rate outside the range of 12-16 breaths/min
26. [26] Axillary body temperature outside the interval of 35.5 to 37.1°C
27. [27] Any clinically significant abnormality of the resting ECG (12-lead)
28. [28] Laboratory values outside normal range with clinical relevance
29. [29] Special diet due to any reason, e.g. vegetarians
30. [30] Subjects who are known or suspected: - not to comply with the study directives; - not to be reliable or trustworthy; - not to be capable of understanding and evaluating the information given to them as part of the formal information policy (informed consent), in particular regarding the risks and discomfort to which they would agree to be exposed; - to be in such a precarious financial situation that they no longer weigh up the possible risks of their participation and the unpleasantness they may be involved in - subject is in custody or submitted to an institution due to a judicial order.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The pharmacokinetic (PK) endpoints in the present trial are Cmax, Tmax, AUC(0-4h), AUC(0-t), AUC(0-∞), t½ of levodopa.

Secondary endpoints 1

1. The safety endpoints in this trial are the clinical and laboratory examinations and registration of adverse events, clinical biochemistry, hematology, urinalysis, physical examination, vital signs (pre- and post-dose).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

CCDRD Cooperative Clinical Drug Research and Development AG

Sponsor organisation

CCDRD Cooperative Clinical Drug Research and Development AG

Address

Lindenallee 70, Dahlwitz-Hoppegarten Dahlwitz-Hoppegarten

City

Hoppegarten

Postcode

15366

Country

Germany

Scientific contact point

Organisation

CCDRD Cooperative Clinical Drug Research and Development AG

Contact name

Sacha Arsova, PhD

Public contact point

Organisation

CCDRD Cooperative Clinical Drug Research and Development AG

Contact name

Sacha Arsova, PhD

PureIMS B.V.

Sponsor organisation

PureIMS B.V.

Address

Ceintuurbaan Noord 152

City

Roden

Postcode

9301 NZ

Country

Netherlands

Scientific contact point

Organisation

PureIMS B.V.

Contact name

Marcel Hoppentocht, PhD

Public contact point

Organisation

PureIMS B.V.

Contact name

Marcel Hoppentocht, PhD

Sponsor responsibilities

Contact point sponsor

CCDRD Cooperative Clinical Drug Research and Development AG

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 2 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications