Safety, Tolerability and Pharmacokinetics After Continuous Infusion of KAND567

NCT06030375 | Completed Phase 1 DMC

• 2 other identifiers: KAN00042019-004585-18
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

The study was planned to consist of 24 healthy subjects in 3 dosing cohorts receiving a continuous i.v. infusion of KAND567 or placebo for 6 h (6 subjects on active and 2 subjects on placebo per cohort), with the option of two additional cohorts of the same size and group composition.

Conditions

Healthy

Outcome Measures

Primary Outcomes (9)

• Safety and tolerability after continuous infusion of KAND567, as measured by adverse events (AEs)

  Measured by the occurrence of AEs and serious adverse events (SAEs)

  From the first IMP administration (Day 1) until the last follow-up visit (Day 30)

• Safety and tolerability after continuous infusion of KAND567, as measured by vital signs

  Measured by the occurrence of clinically abnormal vital signs

  From the first IMP administration (Day 1) until the last follow-up visit (Day 30)

• Safety and tolerability after continuous infusion of KAND567, as measured by ECG

  Measured by the occurrence of clinically abnormal electrocardiography (ECG)

  From the first IMP administration (Day 1) until the last follow-up visit (Day 30)

• Safety and tolerability after continuous infusion of KAND567, as measured by lab safety tests

  Measured by the occurrence of clinically abnormal lab test results (routine clinical chemistry, haematology, and urinalysis)

  From the first IMP administration (Day 1) until the last follow-up visit (Day 30)

• Pharmacokinetics (PK) after continuous infusion of KAND567, as measured by Css

  Measured by plasma drug concentration at steady state (Css)

  From the first IMP administration (Day 1) until Day 2

• Pharmacokinetics (PK) after continuous infusion of KAND567, as measured by AUC

  Measured by the area under the plasma concentration-time curve (AUC)

  From the first IMP administration (Day 1) until Day 2

• Pharmacokinetics (PK) after continuous infusion of KAND567, as measured by t1/2z

  Measured by terminal half-life (t1/2z)

  From the first IMP administration (Day 1) until Day 2

• Pharmacokinetics (PK) after continuous infusion of KAND567, as measured by Vss

  Measured by the apparent volume of distribution at steady state (Vss)

  From the first IMP administration (Day 1) until Day 2

• Pharmacokinetics (PK) after continuous infusion of KAND567, as measured by CL

  Measured by the systemic clearance (CL)

  From the first IMP administration (Day 1) until Day 2

Study Arms (2)

KAND567 in ascending doses

ACTIVE COMPARATOR

In each of the 3 cohorts, 6 subjects were planned to be randomised to receive KAND567. The dose levels were 33.8 mg/6 h (cohort 1), 67 mg/6 h (cohort 2), or 134 mg/6 h (cohort 3).

Drug: KAND567

Placebo

PLACEBO COMPARATOR

In each of the 3 cohorts, 2 subjects were planned to be randomised to receive Placebo.

Other: Placebo

Interventions

KAND567 DRUG

Continuous intravenous infusion for 6 hours

KAND567 in ascending doses

Placebo OTHER

Continuous intravenous infusion for 6 hours

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of written informed consent prior to any study specific procedures
• Body weight \> 50 kg
• Body Mass Index (BMI) ≥ 19 and ≤ 30 kg/m\^2 at screening
• Healthy male and female subjects aged ≥ 18 and ≤ 65 years at screening
• Male subjects must agree to use an adequate method of contraception. Male subjects who are heterosexually active must use, with their partner, a condom AND one of the following methods of highly effective contraception from the time of IMP administration until 90 days after dosing of IMP.
• oral (except low-dose gestagen (lynestrenol and norestisteron)), injectable or implanted hormonal contraceptives
• intrauterine device
• intrauterine system (for example progestin-releasing coil)
• vasectomized male (with appropriate post vasectomy documentation of the absence of sperm in the ejaculate)
• bilateral tubal occlusion or hysterectomy
• Female subject must be of non-childbearing potential (defined as pre-menopausal females with a documented tubal ligation or hysterectomy or bilateral oophorectomy; or as post-menopausal females defined as 12 months' amenorrhoea \[in questionable cases a blood sample with simultaneous follicle stimulating hormone 25-140 IE/L and estradiol \< 200 pmol/L is confirmatory\])
• Willingness and ability to comply with study procedures, visit schedules, study restrictions and requirements

You may not qualify if:

• Present or known history of clinically significant cardio- or cerebrovascular, pulmonary, renal, hepatic, neurological, mental, metabolic, endocrine, haematological, gastrointestinal disorder, significant respiratory disease, sleep apnoea, narcolepsy or any other major disorder that may interfere with the objectives of the study, as judged by the investigator
• Any clinically significant abnormalities in physical examination, electrocardiogram (ECG; e.g. QTcF\>450 ms), clinical chemistry, haematology or urinalysis results at screening, as judged by the investigator
• Clinically significant abnormal blood pressure (treated or untreated), defined as systolic pressure above or equal to 160 mmHg and/or diastolic blood pressure above or equal to 90 mmHg at screening
• Pulse rate \< 45 bpm at screening
• Clinically significant illness within the 5 days prior to the administration of the IMP
• Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody or human immunodeficiency virus (HIV)
• Known or suspected drug or alcohol abuse or positive screen for drugs of abuse test or positive alcohol breath test at screening visit or any time prior to randomisation
• Smoking \> 5 cigarettes per day, or inability to refrain from smoking or using other nicotine-containing products during the stay at the study centre.
• Subject who has received any investigational drug within the last 3 months before administration of IMP
• Plasma donation within one month of screening visit, or any blood donation/ blood loss \> 450 mL during the 3 months prior to screening visit
• Use of the herbal remedy St. John's Wort within two weeks prior to the first dose of the IMP (induces cytochrome P450-3A4)
• Use of prescribed medication during the two weeks prior to the administration of the IMP (or longer if the prescribed medication has a half-life long enough to potentially expose the subject to any significant systemic exposure, as judged by the investigator)
• Use of over-the-counter drugs (including herbals (St. John's Wort - see above), vitamins and minerals) during one week prior to the administration of the IMP or need for concomitant medication during the study. However, occasional paracetamol for pain relief is allowed (up to 3 g per 24 hours)
• Female subjects: Positive pregnancy test at screening visit or at any time prior to randomisation
• Investigator considers the subject unlikely to comply with study procedures, restrictions and requirements

Sponsors & Collaborators

• Novakand Pharma AB: lead

Study Sites (1)

Clinical Research Services Turku (CRST)

Turku, 20520, Finland

Location

Study Officials

• Mika Scheinin, MD, PhD

  Clinical Research Services Turku (CRST)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The physical appearance of the KAND567 solution is a clear transparent solution with a distinct smell. An unblinded pharmacist or registered nurse at the study centre therefore prepared the dosing solutions. There were two unblinded persons working together, one person handled the IMP and perform the dispensing according to the randomisation list and the other person monitored the process.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 24, 2023
• First Posted: September 11, 2023
• Study Start: February 17, 2020
• Primary Completion: April 27, 2020
• Study Completion: April 27, 2020
• Last Updated: September 11, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

FI (1)