Clinical trial NCT06360640: A First-in-human Trial to Evaluate Safety, Tolerability, and Pharmacokinetics of APC148 in Healthy Adults
Official title: A First-in-human, Randomised, Double-blind, Placebo-controlled, Single Ascending Dose Trial to Evaluate Safety, Tolerability, and Pharmacokinetics of APC148 in Healthy Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Lead sponsor: AdjuTec Pharma AS
Sponsor class: INDUSTRY
Collaborators: name: CTC Clinical Trial Consultants AB
First posted: 2024-04-11
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Placebo-controlled, 6 sequential cohorts.
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this first-in-human trial is to investigate the safety, tolerability, and pharmacokinetics of APC148 after intravenous (IV) infusion of single ascending doses in healthy adults.

Detailed description: Participants will receive a single 3-hours IV infusion of APC148 or placebo. 6 sequential cohorts are planned. The first 2 subjects in each cohort will be dosed in a sentinel fashion. The subjects will be followed for 7 days.

Eligibility criteria: Inclusion Criteria:

* Willing and able to give written informed consent for participation in the trial.
* Healthy females of non-childbearing potential and healthy males aged ≥18 and ≤60 years at the time of the screening visit.
* BMI ≥ 18.5 and ≤ 30.0 at the time of the screening visit, and body weight of ≥50 and ≤100 kg.
* Medically healthy participant without abnormal clinically significant medical history, physical findings, vital signs, ECG and laboratory values at the time of the screening visit, as judged by the Investigator.
* Male participants must be willing to use condom or be vasectomised or practice sexual abstinence from heterosexual intercourse and refrain from donating sperm from the administration of investigational medicinal product (IMP) until 3 months after the administration of IMP. Any female partner of a non-vasectomised male participant who is of child-bearing potential must use a highly effective method of contraception with a failure rate of \<1 % to prevent pregnancy from at least 2 weeks prior to the administration of IMP to 3 months after the administration of IMP.
* Women of non-childbearing potential.
* Adequate renal function at the screening visit: Creatinine estimated glomerular filtration rate (eGFR) ≥80 mL/min/1.73 m2 for participants aged 18-50 years and eGFR ≥60 mL/min/1.73 m2 for participants ≥51 years and S-creatinine ≤ upper limit of normal.

Exclusion Criteria:

* History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the participant at risk because of participation in the trial, or influence the results or the participant's ability to participate in the trial.
* History of kidney disease or renal stone.
* Any clinically significant illness, medical/surgical procedure or trauma within 4 weeks of the administration of IMP.
* Malignancy within the past 5 years, with the exception of in situ removal of basal cell carcinoma.
* Any planned major surgery within the duration of the trial.
* After 10 minutes supine rest at the screening visit, any vital signs values outside the following ranges:

  * Systolic blood pressure: \<90 or ≥140 mmHg, or
  * Diastolic blood pressure \<50 or ≥90 mmHg, or
  * Pulse \<40 or \>90 bpm
* A mean QTcF (QT corrected for heart rate by Fredericia's formula) interval of \>450 ms after triplicate measurements. The average of the 3 QTc(F) values will be used to determine the participant's eligibility.
* 12-lead ECG:

  * with PR interval shortening \< 120 ms.
  * PR \> 110 ms but \< 120 ms is acceptable if there is no evidence of ventricular pre- excitation OR
  * PR interval prolongation \> 220 ms OR
  * Intermittent second or third degree atrioventricular (AV) block, or AV dissociation
* History of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmias or torsades de pointes, structural heart disease, or a family history of Long QT Syndrome.
* History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the Investigator, or history of hypersensitivity to drugs with a similar chemical structure or class to APC148.
* Regular use of any prescribed or non-prescribed medications, including antacids, analgesics, herbal remedies, vitamins and minerals, within 2 weeks prior to the administration of IMP, except occasional intake of paracetamol (maximum 2000 mg/day and not exceeding 3000 mg/week), as well as nasal decongestants without cortisone, antihistamine or anticholinergics for a maximum of 10 days, at the discretion of the Investigator.
* Any positive result at the screening visit for serum hepatitis B surface antigen, hepatitis B/C antibodies and/or HIV.
* Positive result for drugs of abuse or alcohol at the screening visit or on admission to the trial site prior to the administration of the IMP.
* Planned treatment or treatment with another investigational drug within 3 months prior to Day -1. Participants consented and screened but not dosed in previous Phase I trials are not to be excluded.
* Current smokers or users of nicotine products. Irregular use of nicotine (e.g., smoking, snuffing, chewing tobacco) less than 3 times/week is allowed before the screening visit.
* History of, or current, drug abuse, use of anabolic steroids, alcohol abuse or excessive intake of alcohol, as judged by the Investigator.
* Excessive caffeine consumption defined by a daily intake of \> 5 cups (1 cup = approximately 240 mL) of caffeine containing beverages, as judged by the Investigator.
* Plasma donation within 1 month of the IMP infusion or blood donation (or corresponding blood loss) during the last 3 months prior to the IMP infusion.
* Participated in a previous cohort in the trial.
* The Investigator considers the participant unlikely to comply with trial procedures, restrictions, and requirements.

Primary outcomes:
measure: Incidence and intensity of adverse events (AEs)
timeFrame: From start of infusion until end of trial visit Day 8
measure: Incidence and intensity of serious adverse events (SAEs)
timeFrame: From start of infusion until end of trial visit Day 8
measure: Incidence and intensity of infusion-related AEs
timeFrame: From start of infusion until end of trial visit Day 8
measure: Time course of local tolerability reactions
timeFrame: Pre-dose, Day 1, Day 2 and Day 8
measure: Changes from baseline in blood pressure
timeFrame: Day -1, Day 1, Day 2, Day 3 and Day 8
measure: Changes from baseline in respiratory rate
timeFrame: Day -1, Day 1, Day 2, Day 3 and Day 8
measure: Changes from baseline in body temperature
timeFrame: Day1, Day 2, Day 3 and Day 8
measure: Changes from baseline in heart rate
timeFrame: Day -1, Day 1, Day 2, Day 3 and Day 8
measure: Changes from baseline in PQ/PR interval
timeFrame: Day -1, Day 1, Day 2, Day 3 and Day 8
measure: Changes from baseline in QRS interval
timeFrame: Day -1, Day 1, Day 2, Day 3 and Day 8
measure: Changes from baseline in QT interval
timeFrame: Day -1, Day 1, Day 2, Day 3 and Day 8
measure: Changes from baseline in QTcF interval
timeFrame: Day -1, Day 1, Day 2, Day 3 and Day 8
measure: Changes from baseline in Clinical Laboratory Profile
timeFrame: Day -1, Day 1, Day 2, Day 3 and Day 8
measure: Changes from baseline in physical examination
timeFrame: Day -1, Day 1, Day 3 and Day 8
Secondary outcomes:
measure: APC148 plasma concentrations
timeFrame: Day 1, Day 2 and Day 3
measure: APC148 urine concentrations
timeFrame: Day 1 and Day 2
measure: Pharmacokinetic (PK) parameter in plasma - Area under curve (AUC) 0-24
timeFrame: Day 1, Day 2, Day 3
measure: PK parameter in plasma - AUC0-inf
timeFrame: Day 1, Day 2, Day 3
measure: PK parameter in plasma - AUC0-last
timeFrame: Day 1, Day 2, Day 3
measure: PK parameter in plasma - Cmax
timeFrame: Day 1, Day 2, Day 3
measure: PK parameter in plasma - Tmax
timeFrame: Day 1, Day 2, Day 3
measure: PK parameter in plasma - T1/2
timeFrame: Day 1, Day 2, Day 3
measure: PK parameter in plasma - Clearance (CL)
timeFrame: Day 1, Day 2, Day 3
measure: PK parameter in plasma - Vz
timeFrame: Day 1, Day 2, Day 3
measure: PK parameter in plasma - Vss determination of plasma concentrations will be collected.
timeFrame: Day 1, Day 2, Day 3
measure: PK parameters in urine - A(e)
timeFrame: Day 1 and Day 2
measure: PK parameters in urine - fe
timeFrame: Day 1 and Day 2
measure: PK parameter in urine - renal clearance (CLr)
timeFrame: Day 1 and Day 2
Other outcomes:
Locations:
city: Uppsala
country: Sweden
facility: Clinical Trial Consultants AB
Study officials:
affiliation: Clinical Trial Consultants AB (CTC)
name: Erik Rein-Hedin, MD
role: PRINCIPAL_INVESTIGATOR
References: