A study to learn how well the drug AKST4290 works and how safe AKST4290 is in people who have Parkinson's disease that are taking dopamine based medication.

• Register: EUCTR
• Last refreshed on: 5 April 2021
• Main ID: EUCTR2019-001657-42-DE
• Date of registration: 11/06/2019
• Prospective Registration: Yes
• Primary sponsor: Alkahest, Inc.
• Public title: A study to learn how well the drug AKST4290 works and how safe AKST4290 is in people who have Parkinson's disease that are taking dopamine based medication.
• Scientific title: A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of AKST4290 in Subjects with Parkinson's Disease on Stable Dopaminergic Treatment - N/A
• Date of first enrolment: 22/10/2019
• Target sample size: 120
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2019-001657-42
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Estonia, Germany, Hungary, Poland, Slovakia, United States

Contacts

• Name: Esther Rawner
• Affiliation: Alkahest, Inc.

• Name: Esther Rawner
• Affiliation: Alkahest, Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Aged 50-80 years at time of enrollment, inclusive.
2. Diagnosis of clinically established or clinically probable Parkinson's Disease (PD) according to MDS-PD criteria with at least 1 year of PD symptoms.
3. Modified Hoehn and Yahr =2.5.
4. Have notable motor worsening during off-medication state.
5. Must be on stable dopaminergic therapy.
6. If on medications for cognition,must be on stable dosage for at least 8 weeks.
7. If on antidepressant medications or neuroleptic medications, must be on stable dosage for at least 8 weeks prior to enrollment.
8. Female subjects must not be pregnant or breastfeeding. Women of childbearing potential (WOCBP) must have a negative pregnancy test at Screening. WOCBP must agree to use highly effective contraception which includes combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion or vasectomized partner prior to study entry. A woman is considered of childbearing potential following menarche and until becoming postmenopausal (no menses for at least 2 years without an alternative cause). Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in the study, she should inform her treating physician immediately. Male subjects must be willing to use a barrier method contraception.
09. The subject must be able to understand the procedures and agree to complete the required assessments.
10. Provide a signed and dated informed consent form in accordance with local regulations and/or IRB/IEC guidelines.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 36
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 84

Exclusion criteria:
1. Secondary or atypical parkinsonian syndromes.
2. Medical history or condition:
• Uncontrolled diabetes mellitus.
• Myocardial infarction or stroke within 12 months of screening.
• Significant cardiac arrhythmia.
• Active bleeding disorder.
• Concomitant use of warfarin or oral anticoagulation therapy.
• Major surgery within 1 month of screening or planned within the study.
• Active liver disease.
• Uncontrolled high blood pressure.
• Known infection with hepatitis B virus, hepatitis C virus, or human immunodeficiency virus (HIV).
3. Prior treatment within 2 weeks or planned use of potent cytochrome P450 3A4/5 (CYP3A4/5) or P glycoprotein (P-gp) inhibitors or inducers
during the study)
4. Current or planned concomitant use of drugs that are P-gp sensitive substrates/P-gp narrow therapeutic index (NTI) substrates (e.g., some
factor Xa inhibitors)
5. Current or planned concomitant use of warfarin.
6. Renal function as defined by estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m2 using the Modification of Diet in Renal
Disease (MDRD) study equation.
7. Use of any nonselective monoamine oxidase (MAO) inhibitors.
8. Current or planned concomitant use of clozapine
9. History of any brain surgery for Parkinson's Disease .
10. Use of systemic steroids.
11. History of any brain surgery for Parkinson's Disease .
12. Use of systemic steroids.
13. Based on ECG reading, subjects with a risk of QT prolongation including:
• The use of concomitant medications known to prolong the QT/QTc interval.
14. Significant medical conditions
15. Malignancy for which the patient has undergone resection, radiation or chemotherapy within past 5 years.
16. Concurrent participation in another interventional clinical trial.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Parkinson's Disease
MedDRA version: 20.0 Level: PT Classification code 10061536 Term: Parkinson's disease System Organ Class: 10029205 - Nervous system disorders

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Product Name: AKST4290
Product Code: AKST4290
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: AKST4290
CAS Number: 1372127-19-9
Current Sponsor code: AKST4290
Other descriptive name: 2-[[[(2R)-1-[1-[(4-CHLORO-3-METHYLPHENYL)METHYL]-4- PIPERIDINYL]-5-OXO-2-PYRROLIDINYL]CARBONYL]AMINO]- N,N,6-TRIMETHYL-4-PYRIDINECARBOXAMIDE,DIHYDROCHLORIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: To assess the effects of AKST4290 on motor function in the practically defined off-medication state in subjects with Parkinson's Disease

Secondary Objective: To assess the safety of AKST4290 in subjects with Parkinson's Disease as well as the potential effects on clinical funtion, cognition and activities of daily living

Primary end point(s): Change from Baseline (Day 1) in motor function during the practically defined off-medication state, defined as greater than or equal to 12 hours off levodopa as measured by the MDS-UPDRS Part 3

Timepoint(s) of evaluation of this end point: Week 12 (Day 84)

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 12 (Day 84)

Secondary end point(s): 1. Incidence of treatment-emergent Adverse Events and Serious Adverse Events identidied by Medical Dictionary for Regulatory Activities Preferred Term (MedDRA PT) and grouped by MedDRA System Organ Class (SOC)
2. Incidence of abnormalities or clinically-significant changes from Baseline in laboratory test data, vital sign measurements, and electrocardiogram's
3. Change from baseline (Day 1) in clinical function, motor function, and activities of daily living at Week 12 (Day 84) during the on-medication state as assessed by the following:
a. Movement Disorder Society’s Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Parts 1-4
b. Montreal Cognitive Assessment (MoCA)
c. Schwab and England Activities of Daily Living (SE-ADL) Scale
d. Clinical Impression of Severity Index – Parkinson’s Disease (CISI-PD)
e. Parkinson’s Disease Quality of Life Questionnaire-39 (PDQ-39)
f. Sheehan-Suicidality Tracking Scale (S-STS)
g. 10-meter timed walk
h. Hauser 3-Day Patient Diary

Secondary ID(s)

AKST4290-211

Source(s) of Monetary Support

Alkahest, Inc.

Ethics review

Status: Approved
Approval date: 22/10/2019
Contact: