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A Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of anle138b in Parkinson's Disease

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ClinicalTrials.gov Identifier: NCT04685265
Recruitment Status : Recruiting
First Posted : December 28, 2020
Last Update Posted : October 26, 2021
Sponsor:
Collaborators:
Aptuit (Verona) Srl, an Evotec Company
Quotient Sciences
Nottingham University Hospitals NHS Trust
Information provided by (Responsible Party):
MODAG GmbH

Brief Summary:
The purpose of this study is to determine the safety, tolerability and blood levels of orally administered anle138b as well as the effect of food and early signs of efficacy in patients with mild to moderate Parkinson´s disease.

Condition or disease Intervention/treatment Phase
Parkinson Disease Drug: anle138b Drug: Placebo Phase 1

Detailed Description:
This is a two centre, double-blind, randomised, placebo-controlled, multiple ascending dose study in patients with mild to moderate Parkinson´s disease. It is planned to enrol up to 5 cohorts. Cohorts A-C consist of up to 8 subjects; Cohorts D and E will be conducted based on data from Cohorts A-C. Subjects will be randomly assigned to receive multiple ascending oral doses of anle138b or matching placebo (6 active investigational medicinal product [IMP], 2 placebo per cohort) for 7 days in a sequential escalating manner. Subjects in Cohorts A and B will also receive an additional single oral dose of active IMP or matching placebo on Day 9 of the study for an assessment of the effect of food on the PK of anle138b in PD patients.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: This study is double-blind. Treatment assignment will not be known to the subjects, the sponsor or the staff who are involved in the clinical evaluation of the subjects and the analysis of data. The randomisation schedule and disclosure envelopes will be generated by an unblinded statistician at Quotient Sciences.
Primary Purpose: Treatment
Official Title: A Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Ascending Oral Doses of anle138b, and to Characterise the Effect of Food of anle138b in Mild to Moderate Parkinson's Disease
Actual Study Start Date : December 22, 2020
Estimated Primary Completion Date : June 2022
Estimated Study Completion Date : June 2022


Arm Intervention/treatment
Active Comparator: anle138b
150 mg and higher dosage
Drug: anle138b
capsule containing excipient and anle138b

Placebo Comparator: Placebo
Matching placebo dosage
Drug: Placebo
matching placebo capsule containing excipient




Primary Outcome Measures :
  1. Incidence of treatment-emergent adverse events in PD patients with multiple ascending doses of anle138b taken in the fasted state. [ Time Frame: Day 1 to day 30 post dose ]
    Adverse events

  2. Incidence of treatment-emergent adverse events in PD patients with multiple ascending doses of anle138b taken in the fed state (Cohorts A and B). [ Time Frame: Day 1 to day 30 post dose ]
    Adverse events

  3. Incidence of treatment-emergent changes in vital signs in PD patients with multiple ascending doses of anle138b taken in the fasted state. [ Time Frame: Day 1 to day 14 ]
    Blood pressure

  4. Incidence of treatment-emergent changes in vital signs in PD patients with multiple ascending doses of anle138b taken in the fasted state. [ Time Frame: Day 1 to day 14 ]
    Heart rate

  5. Incidence of treatment-emergent changes in vital signs in PD patients with multiple ascending doses of anle138b taken in the fasted state. [ Time Frame: Day 1 to day 14 ]
    Oral temperature

  6. Incidence of treatment-emergent changes in vital signs in PD patients with multiple ascending doses of anle138b taken in the fed state (Cohorts A and B). [ Time Frame: From fed dosing to 48 hours post dosing ]
    Blood pressure

  7. Incidence of treatment-emergent changes in vital signs in PD patients with multiple ascending doses of anle138b taken in the fed state (Cohorts A and B). [ Time Frame: From fed dosing to 48 hours post dosing ]
    Heart rate

  8. Incidence of treatment-emergent changes in vital signs in PD patients with multiple ascending doses of anle138b taken in the fed state (Cohorts A and B). [ Time Frame: From fed dosing to 48 hours post dosing ]
    Oral temperature

  9. Incidence of treatment-emergent ECG changes in PD patients with multiple ascending doses of anle138b taken in the fasted state. [ Time Frame: Day 1 to day 14 ]
    Electrocardiogram (ECG) parameters including QT interval corrected for heart rate using Fridericia's formula (QTcF)

  10. Incidence of treatment-emergent ECG changes in PD patients with multiple ascending doses of anle138b taken in the fed state (Cohorts A and B). [ Time Frame: From fed dosing to 48 hours post dosing ]
    Electrocardiogram (ECG) parameters including QT interval corrected for heart rate using Fridericia's formula (QTcF)

  11. Incidence of treatment-emergent changes in physical examination in PD patients with multiple ascending doses of anle138b taken in the fasted state. [ Time Frame: Day 1 to day 14 ]
    Physical examination findings

  12. Incidence of treatment-emergent changes in physical examination in PD patients with multiple ascending doses of anle138b taken in fed state (Cohorts A and B). [ Time Frame: From fed dosing to 48 hours post dosing ]
    Physical examination findings

  13. Incidence of treatment-emergent changes in clinical laboratory parameters in PD patients with multiple ascending doses of anle138b taken in the fasted state. [ Time Frame: Day 1 to day 14 ]
    Clinical laboratory Tests: Hematology

  14. Incidence of treatment-emergent changes in clinical laboratory parameters in PD patients with multiple ascending doses of anle138b taken in the fasted state. [ Time Frame: Day 1 to day 14 ]
    Clinical chemistry: Renal function tests

  15. Incidence of treatment-emergent changes in clinical laboratory parameters in PD patients with multiple ascending doses of anle138b taken in the fasted state. [ Time Frame: Day 1 to day 14 ]
    Clinical chemistry: Hepatic enzymes

  16. Incidence of treatment-emergent changes in clinical laboratory parameters in PD patients with multiple ascending doses of anle138b taken in the fasted state. [ Time Frame: Day 1 to day 14 ]
    Clinical chemistry: Electrolytes

  17. Incidence of treatment-emergent changes in clinical laboratory parameters in PD patients with multiple ascending doses of anle138b taken in the fasted state. [ Time Frame: Day 1 to day 14 ]
    Clinical chemistry: Creatine kinase

  18. Incidence of treatment-emergent changes in clinical laboratory parameters in PD patients with multiple ascending doses of anle138b taken in fed state (Cohorts A and B). [ Time Frame: From fed dosing to 48 hours post dosing ]
    Clinical laboratory Tests: Hematology

  19. Incidence of treatment-emergent changes in clinical laboratory parameters in PD patients with multiple ascending doses of anle138b taken in fed state (Cohorts A and B). [ Time Frame: From fed dosing to 48 hours post dosing ]
    Clinical chemistry: Renal function tests

  20. Incidence of treatment-emergent changes in clinical laboratory parameters in PD patients with multiple ascending doses of anle138b taken in fed state (Cohorts A and B). [ Time Frame: From fed dosing to 48 hours post dosing ]
    Clinical chemistry: Hepatic enzymes

  21. Incidence of treatment-emergent changes in clinical laboratory parameters in PD patients with multiple ascending doses of anle138b taken in fed state (Cohorts A and B). [ Time Frame: From fed dosing to 48 hours post dosing ]
    Clinical chemistry: Electrolytes

  22. Incidence of treatment-emergent changes in clinical laboratory parameters in PD patients with multiple ascending doses of anle138b taken in fed state (Cohorts A and B). [ Time Frame: From fed dosing to 48 hours post dosing ]
    Clinical chemistry: Creatine kinase


Secondary Outcome Measures :
  1. Oral pharmacokinetics (PK) of multiple ascending doses of anle138b in PD patients taken in the fasted state. [ Time Frame: Day 1 to day 9 ]
    PK parameter: Tlag for anle138b.

  2. Oral pharmacokinetics (PK) of multiple ascending doses of anle138b in PD patients taken in the fasted state. [ Time Frame: Day 1 to day 9 ]
    PK parameter: Tmax for anle138b.

  3. Oral pharmacokinetics (PK) of multiple ascending doses of anle138b in PD patients taken in the fasted state. [ Time Frame: Day 1 to day 9 ]
    PK parameter: Cmax for anle138b.

  4. Oral pharmacokinetics (PK) of multiple ascending doses of anle138b in PD patients taken in the fasted state. [ Time Frame: Day 1 to day 9 ]
    PK parameter: C12 for anle138b.

  5. Oral pharmacokinetics (PK) of multiple ascending doses of anle138b in PD patients taken in the fasted state. [ Time Frame: Day 1 to day 9 ]
    PK parameter: C24 for anle138b.

  6. Oral pharmacokinetics (PK) of multiple ascending doses of anle138b in PD patients taken in the fasted state. [ Time Frame: Day 1 to day 9 ]
    PK parameter: AUC(0-tau) for anle138b.

  7. Oral pharmacokinetics (PK) of multiple ascending doses of anle138b in PD patients taken in the fasted state. [ Time Frame: Day 1 to day 9 ]
    PK parameter: Lambda-z for anle138b.

  8. Oral pharmacokinetics (PK) of multiple ascending doses of anle138b in PD patients taken in the fasted state. [ Time Frame: Day 1 to day 9 ]
    PK parameter: T1/2 for anle138b.

  9. Oral pharmacokinetics (PK) of multiple ascending doses of anle138b in PD patients taken in the fasted state. [ Time Frame: Day 1 to day 9 ]
    PK parameter: Accumulation ratio for Cmax (Day 7) for anle138b.

  10. Oral pharmacokinetics (PK) of multiple ascending doses of anle138b in PD patients taken in the fasted state. [ Time Frame: Day 1 to day 9 ]
    PK parameter: Accumulation ratio for AUC (Day 7) for anle138b.

  11. Oral pharmacokinetics (PK) of multiple ascending doses of anle138b in PD patients taken in the fed state (Cohorts A and B). [ Time Frame: From fed dosing to 48 hours post dosing. ]
    PK parameter: Cmax for anle138b.

  12. Oral pharmacokinetics (PK) of multiple ascending doses of anle138b in PD patients taken in the fed state (Cohorts A and B). [ Time Frame: From fed dosing to 48 hours post dosing. ]
    PK parameter: AUC(0-24) for anle138b.

  13. Oral pharmacokinetics (PK) of multiple ascending doses of anle138b in PD patients taken in the fed state (Cohorts A and B). [ Time Frame: From fed dosing to 48 hours post dosing. ]
    PK parameter: AUC(0-tau) for anle138b.

  14. Effect of multiple ascending doses of anle138b on the motor status of PD patients [ Time Frame: Baseline to follow-up visit (day 16 for cohorts A and B; day 14 for cohort C and optional cohorts D and E) ]
    Changes from baseline in the "Movement Disorder Society-sponsored revision of the Unified PD Rating Scale" (MDS-UPDRS) ranging from 0 to 260 points with less points meaning less severity.

  15. Effect of multiple doses of anle138b on the CSF levels of anle138b in PD patients [ Time Frame: single time point 3 hours post dose on dosing day 5 ]
    Quantification of anle138b



Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Males and females with a diagnosis of idiopathic PD as defined by the Movement Disorders Society criteria (either fulfilling criteria for "Clinically Established PD" or for "Clinically Probable PD").
  • Body mass index (BMI) 18.5 to 35.0 kg/m2 as measured at screening.
  • Hoehn and Yahr stage I-III (able to walk unaided).
  • Stable medication for PD for 1 month prior to screening at Quotient and anticipated over the study period.
  • No history of dementia.
  • Must be willing and able to communicate and participate in the whole study.
  • Must provide written informed consent.
  • Must agree to adhere to the contraception requirements defined in the study protocol.

Exclusion Criteria:

  • Subjects who have received any IMP in a clinical research study within the 90 days prior to Day 1.
  • Subjects who are, or are immediate family members of, a study site or sponsor employee.
  • Evidence of current SARS-CoV-2 infection.
  • History of any drug or alcohol abuse in the past 2 years.
  • Regular alcohol consumption in males >21 units per week and females >14 units per week (1 unit = ½ pint beer, or a 25 mL shot of 40% spirit, 1.5 to 2 units = 125 mL glass of wine, depending on type).
  • A confirmed positive alcohol breath test at screening or admission.
  • Current smokers and those who have smoked within the last 12 months. A confirmed breath carbon monoxide reading of greater than 10 ppm at screening or admission.
  • Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months.
  • Females of childbearing potential including those who are pregnant or lactating (all female subjects must have a negative highly sensitive serum or urine pregnancy test). A woman is considered of childbearing potential unless she is permanently sterile (hysterectomy, bilateral salpingectomy, and bilateral oophorectomy) or is postmenopausal (had no menses for 12 months without an alternative medical cause and a serum follicle-stimulating hormone [FSH] concentration ≥40 IU/L).
  • Male subjects with pregnant or lactating partners.
  • Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator or delegate at screening.
  • Clinically significant abnormal clinical chemistry, haematology or urinalysis as judged by the investigator.
  • Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) antibody results.
  • History of clinically significant cardiovascular, renal, hepatic, dermatological, chronic respiratory or gastrointestinal disease or psychiatric disorder, as judged by the investigator.
  • Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients.
  • Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hay fever is allowed unless it is active.
  • Donation of blood or plasma within the previous 3 months or loss of greater than 400 mL of blood.
  • Subjects who are taking, or have taken, any prescribed or over-the-counter drug or herbal remedies other than their regular medication according to the referral letter from NUH, and/or up to 2 g of paracetamol per day and/or HRT, in the 14 days before IMP administration.
  • Subjects who are taking, or have taken, in the 14 days before IMP administration the drug warfarin.
  • Subjects who are taking, or have taken, in the 14 days before IMP administration any drug that is considered to interfere with the objectives of the study, as determined by the concomitant medication oversight committee.
  • Failure to satisfy the investigator of fitness to participate for any other reason.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04685265


Contacts
Layout table for location contacts
Contact: Johannes Levin, MD +49-6734-9622 ext 8000 levin@modag.net
Contact: Armin Giese, MD +49-6734-9622 ext 8000 giese@modag.net

Locations
Layout table for location information
United Kingdom
Quotient Sciences Recruiting
Nottingham, United Kingdom, NG11 6JS
Contact: Nand Singh, BSc, MD, DPM, MFPM    +44 (0)115 974 ext 9000    nand.singh@quotientsciences.com   
Contact: Sue Melbourne, DipNurs    +44 (0)115 931 ext 5120    sue.melbourne@quotientsciences.com   
Sponsors and Collaborators
MODAG GmbH
Aptuit (Verona) Srl, an Evotec Company
Quotient Sciences
Nottingham University Hospitals NHS Trust
Investigators
Layout table for investigator information
Principal Investigator: Nand Singh, BSc, MD, DPM, MFPM Quotient Sciences Mere Way Ruddington Fields Ruddington Nottingham NG11 6JS, UK
Principal Investigator: Jonathan Evans, MD Nottingham University Hospitals NHS Trust
Additional Information:
Publications:

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Responsible Party: MODAG GmbH
ClinicalTrials.gov Identifier: NCT04685265    
Other Study ID Numbers: anle138b-P1-02
2020-004869-38 ( EudraCT Number )
First Posted: December 28, 2020    Key Record Dates
Last Update Posted: October 26, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by MODAG GmbH:
anle138b
alpha-Synuclein
Oligomer modulator
Multiple System Atrophy
Parkinson Disease
Alzheimer Disease
Neurodegenerative diseases
Tauopathies
Amyloid
Additional relevant MeSH terms:
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Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Synucleinopathies
Neurodegenerative Diseases