Clinical trial NCT05368831: Open-label Study to Evaluate the Effects of NST-1024 on the PK of Multiple Drugs in Healthy Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: NorthSea Therapeutics B.V.
Sponsor class: INDUSTRY
First posted: 2022-05-10
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: 15 days
measure: Evaluate the Effects of NST-1024 on the Plasma Concentration (Cmax) of Caffeine, Flurbiprofen, Omeprazole, Metoprolol, and Midazolam in Healthy Male and Female Subjects
timeFrame: 15 days
Secondary outcomes:
measure: Assess Adverse Event (AEs) and Serious Adverse Event (SAEs) to Determine Safety Profile of NST-1024 in Healthy Subjects
timeFrame: 15 days
Other outcomes:
Locations:
city: Leeds
country: United Kingdom
facility: Labcorp Clinical Research Unit Ltd.
Study officials:
References: