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

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

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.

Study Overview

• Status: Completed
• Conditions: Cognitive Disorders
• Intervention / Treatment: Drug: Placebo; Drug: SDI-118

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, B-3000
    • Centre for Clinical Pharmacology, UZ Leuven

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• 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.

Specifically, Part B/PET related inclusion criteria:

• Adequate arterial circulation in both hands (Allen's test).
• MRI scan without clinically significant abnormalities.

Specifically, Part C/FE related inclusion criteria:

• Subjects are not vegetarian and willing to eat a standardized high fat breakfast including butter and bacon.

Exclusion Criteria:

• 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).

Specifically, Part B/PET related exclusion criteria:

• Previous inclusion in a research study and/or medical protocol involving nuclear medicine, PET or radiological investigations with significant radiation burden (a significant radiation burden being defined as International Commission on Radiological Protection (ICRP) category IIb or above: no more than 1 mSv in addition to the natural background radiation in the previous 12 months including the dose from the study).
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SDI-118 Dose 1	Drug: SDI-118; SDI-118 Powder in Capsule
Experimental: SDI-118 Dose 2	Drug: SDI-118; SDI-118 Powder in Capsule
Experimental: SDI-118 Dose 3	Drug: SDI-118; SDI-118 Powder in Capsule
Experimental: SDI-118 Dose 4	Drug: SDI-118; SDI-118 Powder in Capsule
Experimental: SDI-118 Dose 5	Drug: SDI-118; SDI-118 Powder in Capsule
Experimental: SDI-118 Dose 6	Drug: SDI-118; SDI-118 Powder in Capsule
Placebo Comparator: SDI-118 Placebo	Drug: Placebo; Matching Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: AbbVie
• Collaborators: KU Leuven; Syndesi Therapeutics
• Investigators: Principal Investigator: Jan deHoon, MD, UZ Leuven

Study record dates

Study Major Dates

• Study Start (Actual): March 14, 2019
• Primary Completion (Actual): July 29, 2019
• Study Completion (Actual): March 11, 2020

Study Registration Dates

• First Submitted: August 2, 2022
• First Submitted That Met QC Criteria: August 2, 2022
• First Posted (Actual): August 3, 2022

Study Record Updates

• Last Update Posted (Actual): August 3, 2022
• Last Update Submitted That Met QC Criteria: August 2, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders
• Other Study ID Numbers: SYND001; 2018-004022-28 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No