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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04685265
Recruitment Status : Active, not recruiting
First Posted : December 28, 2020
Last Update Posted : October 12, 2022
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. In Cohorts A and B, 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 in cohorts A-C) for 7 days in a sequential escalating manner. Subjects in cohort A and B will be dosed once dialy and subjects in cohort C will be dosed twice a day. 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. Subjects in cohort D will be randomly assigned to receive QD doses of anle138b or matching placebo (placebo vs 150 mg vs 300 mg; 1:1:1) for 7 days in fasted state. Subjects in Cohort E will be randomly assigned to receive QD doses of either 300 mg anle138b or matching placebo (1:1) for 28 days taken in the non-fasted state.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 72 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 : December 2022
Estimated Study Completion Date : December 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 (cohorts A-C + D). [ Time Frame: Day 1 to day 14-16: cohorts A-C; day 1 to week 6 post dosing: cohort D ]
    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: From fed dosing (day 9) to day 12-14 ]
    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 (cohorts A-C + D). [ Time Frame: Day 1 to week 1 post dosing: cohorts A-C; day 1 to week 6 post dosing: cohort D ]
    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 (cohorts A-C + D). [ Time Frame: Day 1 to week 1 post dosing: cohorts A-C; day 1 to week 6 post dosing: cohort D ]
    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 (cohorts A-C + D). [ Time Frame: Day 1 to week 1 post dosing: cohorts A-C; day 1 to week 6 post dosing: cohort D ]
    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 1 week 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 1 week 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 1 week 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 (cohorts A-C + D). [ Time Frame: Day 1 to week 1 post dosing: cohorts A-C; day 1 to week 6 post dosing: cohort D ]
    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 1 week 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 (cohorts A-C + D). [ Time Frame: Day 1 to week 1 post dosing: cohorts A-C; day 1 to week 6 post dosing: cohort D ]
    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 1 week 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 (cohorts A-C + D). [ Time Frame: Day 1 to day 8 ]
    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 (cohorts A-C + D). [ Time Frame: Day 1 to day 8 ]
    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 (cohorts A-C + D). [ Time Frame: Day 1 to day 8 ]
    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 (cohorts A-C + D). [ Time Frame: Day 1 to day 8 ]
    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 (cohorts A-C + D). [ Time Frame: Day 1 to day 8 ]
    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 24 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 24 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 24 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 24 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 24 hours post dosing ]
    Clinical chemistry: Creatine kinase

  23. Incidence of treatment-emergent adverse events in PD patients with multiple ascending doses of anle138b taken 28 days in the non-fasted state (cohort E). [ Time Frame: Day 1 to week 6 post dosing ]
    Adverse events

  24. Incidence of treatment-emergent changes in vital signs in PD patients with multiple ascending doses of anle138b taken 28 days in the non-fasted state (cohort E). [ Time Frame: Day 1 to week 6 post dosing ]
    Blood pressure

  25. Incidence of treatment-emergent changes in vital signs in PD patients with multiple ascending doses of anle138b taken 28 days in the non-fasted state (cohort E). [ Time Frame: Day 1 to week 6 post dosing ]
    Heart rate

  26. Incidence of treatment-emergent changes in vital signs in PD patients with multiple ascending doses of anle138b taken 28 days in the non-fasted state (cohort E). [ Time Frame: Day 1 to week 6 post dosing ]
    Oral temperature

  27. Incidence of treatment-emergent changes in vital signs in PD patients with multiple ascending doses of anle138b taken 28 days in the non-fasted state (cohort E). [ Time Frame: Day 1 to week 6 post dosing ]
    Electrocardiogram (ECG) parameters including QT interval corrected for heart rate using Fridericia's formula (QTcF)

  28. Incidence of treatment-emergent changes in physical examination in PD patients with multiple ascending doses of anle138b taken 28 days in the non-fasted state (cohort E). [ Time Frame: Day 1 to week 6 post dosing ]
    Physical examination findings

  29. Incidence of treatment-emergent changes in clinical laboratory parameters in PD patients with multiple ascending doses of anle138b taken 28 days in the non-fasted state (cohort E). [ Time Frame: Day 1 to 24 hours post dosing ]
    Clinical laboratory Tests: Hematology

  30. Incidence of treatment-emergent changes in clinical laboratory parameters in PD patients with multiple ascending doses of anle138b taken 28 days in the non-fasted state (cohort E). [ Time Frame: Day 1 to 24 hours post dosing ]
    Clinical chemistry: Renal function tests

  31. Incidence of treatment-emergent changes in clinical laboratory parameters in PD patients with multiple ascending doses of anle138b taken 28 days in the non-fasted state (cohort E). [ Time Frame: Day 1 to 24 hours post dosing ]
    Clinical chemistry: Hepatic enzymes

  32. Incidence of treatment-emergent changes in clinical laboratory parameters in PD patients with multiple ascending doses of anle138b taken 28 days in the non-fasted state (cohort E). [ Time Frame: Day 1 to 24 hours post dosing ]
    Clinical chemistry: Electrolytes

  33. Incidence of treatment-emergent changes in clinical laboratory parameters in PD patients with multiple ascending doses of anle138b taken 28 days in the non-fasted state (cohort E). [ Time Frame: Day 1 to 24 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 (cohorts A-C + D). [ 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 (cohorts A-C + D). [ 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 (cohorts A-C + D). [ 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 (cohort B). [ 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 (cohorts A-C + D). [ 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 (cohorts A-C + D). [ 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 (cohorts A-C + D). [ 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 (cohorts A-C + D). [ 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 (cohorts A-C + D). [ 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 (cohorts A-C + D). [ 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. Effect of multiple ascending doses of anle138b on the motor status of PD patients [ Time Frame: Admission to follow-up visit (days 14-16 for cohorts A and B; days 12-14 for cohort C; week 6 for 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.

  14. 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 (cohort B) ]
    Quantification of anle138b

  15. Oral pharmacokinetics (PK) of multiple ascending doses of anle138b in PD patients taken in the non-fasted state (cohort E) [ Time Frame: Day 1 to day 30 ]
    PK parameter: Tlag for anle138b

  16. Oral pharmacokinetics (PK) of multiple ascending doses of anle138b in PD patients taken in the non-fasted state (cohort E) [ Time Frame: Day 1 to day 30 ]
    PK parameter: Tmax for anle138b

  17. Oral pharmacokinetics (PK) of multiple ascending doses of anle138b in PD patients taken in the non-fasted state (cohort E) [ Time Frame: Day 1 to day 30 ]
    PK parameter: Cmax for anle138b

  18. Oral pharmacokinetics (PK) of multiple ascending doses of anle138b in PD patients taken in the non-fasted state (cohort E) [ Time Frame: Day 1 to day 30 ]
    PK parameter: C12 for anle138b

  19. Oral pharmacokinetics (PK) of multiple ascending doses of anle138b in PD patients taken in the non-fasted state (cohort E) [ Time Frame: Day 1 to day 30 ]
    PK parameter: C24 for anle138b

  20. Oral pharmacokinetics (PK) of multiple ascending doses of anle138b in PD patients taken in the non-fasted state (cohort E) [ Time Frame: Day 1 to day 30 ]
    PK parameter: AUC(0-tau) for anle138b

  21. Oral pharmacokinetics (PK) of multiple ascending doses of anle138b in PD patients taken in the non-fasted state (cohort E) [ Time Frame: Day 1 to day 30 ]
    PK parameter: Lambda-z for anle138b

  22. Oral pharmacokinetics (PK) of multiple ascending doses of anle138b in PD patients taken in the non-fasted state (cohort E) [ Time Frame: Day 1 to day 30 ]
    PK parameter: T1/2 for anle138b

  23. Oral pharmacokinetics (PK) of multiple ascending doses of anle138b in PD patients taken in the non-fasted state (cohort E) [ Time Frame: Day 1 to day 30 ]
    PK parameter: Accumulation ratio for Cmax for anle138b

  24. Oral pharmacokinetics (PK) of multiple ascending doses of anle138b in PD patients taken in the non-fasted state (cohort E) [ Time Frame: Day 1 to day 30 ]
    PK parameter: Accumulation ratio for AUC for anle138b



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   40 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 or 18.5 to <40.0 kg/m2 (Cohorts D and E) 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 (Cohorts A to C only).
  • Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months (Cohorts A to C only).
  • 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 coagulation (Cohort E only), 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.
  • Subjects who have participated in Cohorts A to C of this study will not be allowed to participate in Cohorts D or E, and subjects who have participated in Cohort D will not be allowed to participate in Cohort E.
  • Failure to satisfy the investigator of fitness to participate for any other reason.
  • Subjects who have a new headache with features suggestive of raised intracranial pressure, including papilloedema, vomiting, posture-related headache, or headache on waking from sleep (Cohort E only).
  • Subjects who have a new headache with focal neurological symptoms, or non-focal neurological symptoms such as change in personality or memory, or an unexplained headache that becomes progressively severe, or an unexplained headache in anyone previously diagnosed with cancer (Cohort E only).
  • Medical history or evidence of mass occupying lesion in brain or spinal cord or history of spinal cord injury, which could preclude the procedure of lumbar puncture and CSF collection (Cohort E only).

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


Locations
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United Kingdom
Quotient Sciences
Nottingham, United Kingdom, NG11 6JS
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 12, 2022
Last Verified: October 2022
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