Open-label Study to Evaluate the Effects of NST-1024 on the PK of Multiple Drugs in Healthy Subjects

A Phase 1, Open-label Study to Evaluate the Effects of NST-1024 on the Pharmacokinetics of Caffeine, Flurbiprofen, Omeprazole, Metoprolol, and Midazolam in Healthy Subjects

Phase 1, open label study to evaluate the effects of NST-1024 on the pharmacokinetics (PK) of caffeine (and paraxanthine), flurbiprofen, omeprazole, metoprolol, and midazolam (and 1-hydroxymidazolam) in healthy male and female subjects.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: NST-1024

Detailed Description

Up to 21 subjects will be enroled to ensure that 18 subjects complete the study. All subjects will receive each of the following treatments:

• Day 1: single oral dose of 100 mg caffeine, 50 mg flurbiprofen, 20 mg omeprazole, 100 mg metoprolol, and 2.5 mg midazolam
• Days 8 to 22: oral doses of 200 mg NST-1024 qd multiple-dose regimen
• Day 8: single oral dose of 100 mg caffeine, 50 mg flurbiprofen, 20 mg omeprazole, 100 mg metoprolol, and 2.5 mg midazolam coadministered with an oral dose of 200 mg NST-1024
• Day 21: single oral dose of 100 mg caffeine and 2.5 mg midazolam coadministered with an oral dose of 200 mg NST-1024.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Leeds, United Kingdom
    • Labcorp Clinical Research Unit Ltd.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Males or females, of any race, between 18 and 65 years of age, inclusive.
2. Body mass index between 18.0 and 32.0 kg/m2, inclusive.
3. In good health, determined by no clinically significant findings from medical history, 12 lead ECG, vital signs measurements, and clinical laboratory evaluations (congenital nonhaemolytic hyperbilirubinemia [eg, suspicion of Gilbert's syndrome based on total and direct bilirubin] is not acceptable) at screening and/or check in and from the physical examination at check-in, as assessed by the investigator (or designee).
4. Females will not be pregnant or lactating, and females of childbearing potential and males will agree to use contraception as detailed in Appendix 4.
5. Able to comprehend and willing to sign an Informed Consent Form (ICF) and to abide by the study restrictions

Exclusion Criteria:

• Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, haematological, pulmonary, cardiovascular (CV), gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the investigator (or designee).
• History of febrile illness within 1 week prior to the first dose.
• History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the investigator (or designee).
• History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy and hernia repair will be allowed).
• Confirmed (eg, 2 consecutive measurements) systolic blood pressure >160 or <80 mmHg, diastolic blood pressure >90 or <45 mmHg, and pulse rate >100 or <40 beats per minute.
• Positive hepatitis panel and/or positive human immunodeficiency virus test
• Administration of a coronavirus disease 2019 vaccine in the past 30 days prior to dosing.
• Use or intend to use any medications/products known to alter drug absorption, metabolism, or elimination processes, including over-the-counter and herbal medication, within 30 days prior to dosing, unless deemed acceptable by the investigator (or designee).
• Use or intend to use any prescription medications/products other than hormone replacement therapy, oral, implantable, transdermal, injectable, or intrauterine contraceptives within 14 days prior to dosing, unless deemed acceptable by the investigator (or designee).
• Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 90 days prior to dosing.
• Alcohol consumption of >21 units (males) and >14 units (females) per week. One unit of alcohol equals ½ pint (285 mL) of beer or lager, 1 glass (125 mL) of wine, or 1/6 gill (25 mL) of spirits.
• Receipt of blood products within 2 months prior to check in.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Oral dose of NST-1024, Caffeine, Flurbiprofen, Omeprazole, Metoprolol, and Midazolam; Day 1: single oral dose of 100 mg caffeine, 50 mg flurbiprofen, 20 mg omeprazole, 100 mg metoprolol, and 2.5 mg midazolam; Days 8 to 22: oral doses of 200 mg NST-1024 qd multiple-dose regimen; Day 8: single oral dose of 100 mg caffeine, 50 mg flurbiprofen, 20 mg omeprazole, 100 mg metoprolol, and 2.5 mg midazolam coadministered with an oral dose of 200 mg NST-1024; Day 21: single oral dose of 100 mg caffeine and 2.5 mg midazolam coadministered with an oral dose of 200 mg NST-1024.

Drug: NST-1024; Drug Drug interactions between NST-1024 and caffeine (and paraxanthine), flurbiprofen, omeprazole, metoprolol, and midazolam

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the Effects of NST-1024 on the AUC0-t vs Time of Caffeine, Flurbiprofen, Omeprazole, Metoprolol, and Midazolam in Healthy Male and Female Subjects	Evaluate the effects of NST-1024 on the pharmacokinetics (PK) (AUC0-t) of caffeine, flurbiprofen, omeprazole, metoprolol, and midazolam in healthy male and female subjects	15 days
Evaluate the Effects of NST-1024 on the Plasma Concentration (Cmax) of Caffeine, Flurbiprofen, Omeprazole, Metoprolol, and Midazolam in Healthy Male and Female Subjects	Evaluate the effects of NST-1024 on the PK (Cmax) of caffeine, flurbiprofen, omeprazole, metoprolol, and midazolam in healthy male and female subjects	15 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess Adverse Event (AEs) and Serious Adverse Event (SAEs) to Determine Safety Profile of NST-1024 in Healthy Subjects	Assess AEs and SAEs to support ongoing safety profile data	15 days

Collaborators and Investigators

• Sponsor: NorthSea Therapeutics B.V.

Study record dates

Study Major Dates

• Study Start (Actual): July 19, 2022
• Primary Completion (Actual): September 7, 2022
• Study Completion (Actual): September 7, 2022

Study Registration Dates

• First Submitted: April 29, 2022
• First Submitted That Met QC Criteria: May 6, 2022
• First Posted (Actual): May 10, 2022

Study Record Updates

• Last Update Posted (Actual): March 8, 2024
• Last Update Submitted That Met QC Criteria: March 6, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: NST-1024-02

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