A Single Ascending Oral Dose Study of SDI-118 in Healthy Male Subjects Including an Assessment of Receptor Occupancy and Food Effect

NCT05486195 | Completed Phase 1

• 2 other identifiers: SYND0012018-004022-28
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This is a First-in-Human, Randomized, Placebo-controlled, Single Ascending Oral Dose Study of SDI-118 in Healthy Male Subjects including Receptor Occupancy Measurements after Single Dose of SDI-118 and an Assessment of Food Effect.

Conditions

Cognitive Disorders

Outcome Measures

Primary Outcomes (9)

• Number of participants with Adverse Events (AEs)

  Adverse events (AEs) will be coded using medical dictionary for regulatory activities (MedDRA). An AE is any untoward medical occurrence in a participant administered a study drug and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medical product whether or not considered related to the medical product. An AE is considered "serious" if, in the view of either the investigator or sponsor, the event: results in death, is life-threatening, results in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, results in congenital anomaly or birth defect, requires hospitalization or prolongation to hospitalization, or other medically important event.

  21 Days

• Number of participants with laboratory value abnormalities and/or adverse events (AEs)

  Number of participants with potentially clinically significant laboratory values (hematology/chemistry/urinalysis)

  21 Days

• Number of participants with vital sign abnormalities and/or adverse events (AEs)

  Number of participants with potentially clinically significant vital sign values

  21 Days

• Number of participants with temperature abnormalities and/or adverse events (AEs)

  Number of participants with potentially clinically significant temperature values

  21 Days

• Number of participants with routine 12 lead electrocardiogram (ECG) abnormalities and/or Adverse Events (AEs)

  Number of participants with potentially clinically significant ECG values.

  21 Days

• Number of participants with routine physical examination abnormalities and/or Adverse Events (AEs)

  Number of participants with potentially clinically significant changes in physical examination.

  21 Days

• Number of participants with routine neurological examination abnormalities and/or Adverse Events (AEs)

  Number of participants with potentially clinically significant changes in neurological examination.

  21 Days

• Number of participants with abnormalities on Profile of Mood States (Brief) and/or Adverse Events (AEs)

  Number of participants with potentially clinically significant changes in Profile of Mood States (Brief) values.

  21 Days

• Number of participants with abnormalities on Bond-Lader-VAS and/or Adverse Events (AEs)

  Number of participants with potentially clinically significant changes in Bond-Lader VAS values.

  21 Days

Study Arms (7)

SDI-118 Dose 1

EXPERIMENTAL

Drug: SDI-118

SDI-118 Dose 2

EXPERIMENTAL

Drug: SDI-118

SDI-118 Dose 3

EXPERIMENTAL

Drug: SDI-118

SDI-118 Dose 4

EXPERIMENTAL

Drug: SDI-118

SDI-118 Dose 5

EXPERIMENTAL

Drug: SDI-118

SDI-118 Dose 6

EXPERIMENTAL

Drug: SDI-118

SDI-118 Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

SDI-118 DRUG

SDI-118 Powder in Capsule

SDI-118 Dose 1; SDI-118 Dose 2; SDI-118 Dose 3; SDI-118 Dose 4; SDI-118 Dose 5; SDI-118 Dose 6

Placebo DRUG

Matching Placebo

SDI-118 Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male subjects, 18 to 50 years of age, inclusive.
• Non-smokers or abstinence from tobacco for at least 3 months prior to screening.
• Body mass index (BMI) between 18 and 30 kg/m2, inclusive, with a minimum weight of 50 kg and maximum of 100 kg.
• Venous access sufficient to allow blood sampling as per the protocol.
• Agree to abstain from alcohol intake 24h before each administration of study drug, during the in-patient period of the study and 24 hours prior to all other out-patient clinic visits.
• Have given written informed consent approved by the relevant Ethics Committee (EC) governing the site.
• In the Investigator's opinion, subject is able to understand the nature of the study and any risks involved in participation, and willing to cooperate and comply with the clinical study protocol restrictions and requirements.
• Subjects and their partners of childbearing potential must be willing to use 2 methods of contraception, one of which must be a barrier method, for the duration of the study and up to 90 days after the last dose.
• Adequate arterial circulation in both hands (Allen's test).
• MRI scan without clinically significant abnormalities.
• Subjects are not vegetarian and willing to eat a standardized high fat breakfast including butter and bacon.

You may not qualify if:

• History or symptoms of any significant disease including (but not limited to), neurological, psychiatric, endocrine, cardiovascular, respiratory, gastrointestinal (GI), hepatic, or renal disorder.
• Positive Hepatitis B surface antigen (HBs Ag), Hepatitis C antibody (HCV Ab), or human immunodeficiency virus antibody (HIV Ab) at screening.
• Use of any medications (prescription or over-the-counter (OTC)), vitamin, mineral, herbal, and dietary supplements (including grapefruit products) within 7 days of study drug administration, or less than 5 half-lives (whichever is longer).
• Have an estimated Glomerular Filtration Rate (eGFR) \<80 mL/min/1.73m2.
• Any of the following findings in the resting ECG:
• QTcF\> 450 or \< 300 msec at screening or baseline visit,
• Notable resting bradycardia (HR \< 40 bpm) or tachycardia (HR \> 100 bpm) at screening or baseline visit,
• Personal or family history of congenital long QT syndrome or sudden death,
• Screening or baseline ECG with QRS and/or T wave judged to be unfavourable for a consistently accurate QT measurement (e.g. neuromuscular artefact that cannot be readily eliminated, arrhythmias, indistinct QRS onset, low amplitude T wave, merged T- and U-waves, prominent U waves),
• Evidence of atrial fibrillation, atrial flutter, Left Bundle Branch Block (LBBB), Wolf-Parkinson-White Syndrome, or cardiac pacemaker at screening or baseline visit (note: a first degree heart block with PR not exceeding 250 msec can be allowed).
• Subject who fulfils any of the MRI contraindications on the standard radiography screening questionnaire (including the presence of ferromagnetic metal in the body or heart pacemaker).
• History of or suffers from claustrophobia or feels that they will be unable to lie still on their back in the PET camera for a period of 2 hours.
• Any known allergy to local anaesthetics or heparin.

Sponsors & Collaborators

• AbbVie: lead
• Syndesi Therapeutics: collaborator
• KU Leuven: collaborator

Study Sites (1)

Centre for Clinical Pharmacology, UZ Leuven

Leuven, B-3000, Belgium

Location

Related Publications (1)

• Botermans W, Koole M, Van Laere K, Savidge JR, Kemp JA, Sunaert S, Duffy MM, Ramael S, Cesura AM, D'Ostilio K, Gossen D, Madsen TM, Lodeweyckx T, de Hoon J. SDI-118, a novel procognitive SV2A modulator: First-in-human randomized controlled trial including PET/fMRI assessment of target engagement. Front Pharmacol. 2023 Jan 17;13:1066447. doi: 10.3389/fphar.2022.1066447. eCollection 2022.

  PMID: 36733374 DERIVED

MeSH Terms

Conditions

Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Officials

• Jan deHoon, MD

  UZ Leuven

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2022
• First Posted: August 3, 2022
• Study Start: March 14, 2019
• Primary Completion: July 29, 2019
• Study Completion: March 11, 2020
• Last Updated: August 3, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)