Clinical Trial of Intranasal Delivery of NT-301 (APPROVE)

Nano PharmaSolutions Australia

Status and phase: Not yet enrolling; Phase 1

Conditions: Safety of NT-301 Nasal Spray; Tolerability of NT-301 Nasal Spray; Performance of NT-301 Nasal Spray Device; Pharmacokinetics of NT-301 Nasal Spray

Treatments: Combination Product: Placebo 1 mg; Combination Product: NT-301 2 mg; Combination Product: Placebo 2 mg; Combination Product: BA NT-301 Nasal spray; Combination Product: NT-301 3 mg; Combination Product: Placebo 3 mg; Drug: Movapo pen; Combination Product: Placebo 4 mg; Combination Product: NT-301 1 mg; Combination Product: NT-301 4 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT06954428

NT-301-101

Details and patient eligibility

About

The purpose of this research project is to investigate the safety and tolerability of an approved drug (Apomorphine) when administered as a nasal powder spray formulation (NT-301) as well as collect information on how NT-301 moves into, through and out of your body, called Pharmacokinetics. The study also aims to compare the safety, tolerability and pharmacokinetics of NT-301 to an injectable Apomorphine product (Movapo Pen), already approved for use in Australia.

Full description

The study will be conducted in two parts:

Part 1: Single Ascending Dose (SAD)- 4 groups will receive a single dose only. Each group receiving a dose higher than the previous cohort. Some participants will get a nasal spray containing NT-301 and others will get a placebo.

Part 2: Comparison PK study- 2 groups to receive 1 dose of NT-301 and a second single dose of approved medication (Apomorphine injection).

Enrollment: 48 estimated patients

Sex: All

Ages: 18 to 60 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Male or female participants aged between 18 and 60 years of age, inclusive at the time of signing the informed consent document.

2. Body weight ≥50 kg and body mass index (BMI) within the range of 18 to 32 kg/m2 inclusive at screening.

3. Woman of childbearing potential (WOCBP) or fertile male participants must agree to use an acceptable method of contraception from the start of Screening until 90 days (male participants) or 60 days (female participants) after the final study visit.

4. WOCBP must have a negative serum pregnancy test at screening and a negative urine pregnancy test prior to administration of the first dose of study intervention (including domperidone) and be willing to have additional pregnancy tests, as required, throughout the study.

5. Participants must be in good general health, as demonstrated at screening and prior to first administration of any study intervention (including domperidone) by the absence of clinically significant (in the opinion of the Investigator) abnormalities based on a medical evaluation including review of medical history, physical examination, safety laboratory tests, vital signs, 12-lead ECG monitoring.

   Note: It is the responsibility of the Investigator to assess the clinical significance of any abnormality/ies; however, consultation with the MM may be warranted.

6. Normal vital signs after ≥5 min resting in supine position:

   1. ≥90 mmHg and ≤160 mmHg systolic blood pressure (SBP)
   2. ≥50 mmHg and ≤95 mmHg diastolic blood pressure (DBP)
   3. ≥ 45 bpm and ≤100 bpm heart rate (HR)
   4. Body temperature (tympanic) ≥35.5°C and ≤37.7°C

7. No clinically significant changes and/or associated symptoms considered related to orthostatic hypotension when measuring blood pressure (BP) and pulse rate (PR) within 2 min of standing from a supine position.

8. Triplicate 12-lead ECG, taken after ≥5 min in a supine, position, with a QT interval corrected using the Fridericia method (QTcF) ≤ 450 msec for males and ≤ 470 msec for females, PR interval ≤ 220 msec or QRS duration ≤ 120 msec or history of long QT syndrome and no clinically significant abnormalities as judged by the Investigator (or qualified designee).

9. Willing and able to be confined at the CRU for the study period and adhere to overall study visit schedule, procedures and other protocol requirements, as assessed by the Investigator (or qualified designee).

10. Understands and voluntarily signs an informed consent document prior to any study related assessments/procedures being conducted.

Exclusion criteria

1. Any significant medical condition, physical or psychiatric illness or history of depression that could, in the Investigator's (or qualified designee) opinion, compromise the participant's safety or interfere with the completion of this study.
2. History of clinically significant CNS, cardiac, pulmonary, metabolic, renal, hepatic, or gastrointestinal (GI) conditions including gastric bypass or other weight loss surgical procedure.
3. Any condition including the presence of laboratory abnormalities, which according to the Investigator (or qualified designee), places the participant at unacceptable risk if they were to participate in the study or may confound the ability to interpret data from the study. This includes the presence of uncontrolled current illness (e.g., an infection), a viral infection, seasonal allergy, or concurrent skin rash.
4. Any nasal condition, including nasal congestion, physical blockage of either nostril, deviated septum, structural or anatomical nasal conditions or nasal surgery in the last 6 months. Use of topical nasal medications (e.g., acute or chronic use of prescription or over the counter nasal sprays) that may affect the administration or absorption of the study drug.
5. Use of 5HT3 antagonists, drugs known to prolong QTc, and use of antihypertensives.
6. The participant has a medical history of or a positive blood test for human immunodeficiency virus (HIV: HIV, anti-HIV1 and anti-HIV2 antibodies), hepatitis C virus (HCV, anti-HCV antibodies), or hepatitis B surface antigen (HBsAg) at screening.
7. Aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl transferase (GGT), serum creatine, or total bilirubin >1.5x the upper limit of normal (ULN). These laboratory tests may be repeated once if they are abnormal on first screening, and if there is a medical reason to believe the results may be inaccurate. If the repeat test is within the normal range, the participant may be included in the study only if the Investigator (or qualified designee) considers that the previous finding will not compromise the participant's safety and will not interfere with the interpretation of safety data.
8. A positive drug or alcohol screen. A positive drug or alcohol screen test result may be verified by re-testing at the discretion of the Investigator (or qualified designee), with up to 1 false positive result permitted.
9. History of regular alcohol consumption within 6 months of screening defined as an average weekly intake of >21 units. One unit is equivalent to 10 g of alcohol and the following can be used as a guide: a half-pint (~240 mL) of beer, 1 glass (125 mL) of wine or 1 (30 mL) measure of spirits.
10. The participant is unwilling to abstain from alcohol consumption from 24 h prior to treatment with any study intervention (including domperidone) and until discharge from the CRU, and for 24 h prior to all other outpatient visits to the CRU.
11. The participant is pregnant or planning to become pregnant within 90 days of the study or is breastfeeding.
12. Major surgery within 4 weeks of screening that could interfere with, or for which the treatment might interfere with, the conduct of the study, or that would pose an unacceptable risk to the participant in the opinion of the Investigator (or qualified designee).
13. Use of tobacco or nicotine products exceeding 5 cigarettes (or equivalent) per week in any form within 30 days prior to treatment with any study intervention (including domperidone), or unwillingness to refrain from smoking, vaping, or using any nicotine products for at least 48 h prior to dosing with any study intervention (including domperidone), the confinement period, and any follow up visits.
14. The participant uses or is planning to use any prescription or non-prescription medications (with the exception of hormonal contraceptives), herbal and dietary supplements, within 5 days or 5 half-lives (whichever is longer) prior to treatment with any study intervention (including domperidone), unless in the opinion of the PI, local MM and Sponsor medical representative, the medication is not expected to interfere with the study procedures or compromise participant safety
15. Participation in a clinical trial and receipt of an investigational medication within 90 days, 5 half-lives (if known) or twice the duration of the biological effect of any medication, whichever is longer, prior to the first dose of study intervention.
16. Use of any strong CYP450-3A4/5 inhibiting or inducing agents within 14 days of dosing with any study intervention (including domperidone) and for the duration of the study.
17. Consumption of grapefruit, grapefruit juice, star fruit, oranges, orange juice, Seville oranges, within 14 days prior to dosing with any study intervention (including domperidone) and participant is unwilling to abstain from consumption of these products until after discharge from the CRU.
18. Participant is unwilling to abstain from the consumption of caffeine and/or xanthine containing products (e.g., coffee, tea, chocolate, and caffeine containing sodas, etc.) from time of admission to the CRU on Day -1 until after discharge from the CRU.
19. Known sensitivity to any study intervention, including NT-301, apomorphine HCl and domperidone.
20. Loss or donation of whole blood (>499 mL) within 3 months and/or plasma donation within 2 weeks, prior to dosing with any study intervention (including domperidone), or intention to donate blood or blood products during the study.
21. The participant has a history of cancer, with the exception of basal cell carcinoma or in situ cervical cancer that has been in remission for ≥5 years prior to first dose of study treatment.
22. Participants with a pre-disposition to nausea and vomiting (e.g., history of severe travel sickness).
23. The participant is unwilling or unable to follow protocol requirements, including domperidone self-administration and diary completion, and attendance at follow up visit(s), or otherwise unsuitable for study participation in the opinion of the Investigator.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Triple Blind

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48 participants in 10 patient groups, including a placebo group

Placebo 1 mg

Placebo Comparator group

Description:

Matching Placebo for 1 mg NT-301

Treatment:

Combination Product: NT-301 1 mg

Combination Product: Placebo 1 mg

Placebo 2 mg

Placebo Comparator group

Description:

Matching placebo for NT-301 2 mg strength

Treatment:

Combination Product: Placebo 2 mg

Combination Product: NT-301 2 mg

NT-301 1 mg

Experimental group

Description:

NT-301 nasal spray 1 mg strength

Treatment:

Combination Product: NT-301 1 mg

NT-301 2 mg

Experimental group

Description:

NT-301 nasal spray 2 mg strength

Treatment:

Combination Product: NT-301 2 mg

Placebo 3 mg

Placebo Comparator group

Description:

Matching placebo for NT-301 3 mg

Treatment:

Combination Product: Placebo 3 mg

Combination Product: NT-301 2 mg

placebo 4 mg

Placebo Comparator group

Description:

Matching placebo for NT-301 4 mg

Treatment:

Combination Product: Placebo 4 mg

Movapo pen

Active Comparator group

Description:

Apomorphine 2 mg sc injection

Treatment:

Drug: Movapo pen

NT-301 3 mg

Active Comparator group

Description:

Apomorphine nasal spray 3 mg

Treatment:

Combination Product: NT-301 3 mg

BA NT-301 strength TBD

Experimental group

Description:

NT-301 apomorphine nasal spray strength TBD

Treatment:

Combination Product: BA NT-301 Nasal spray

NT-301 4 mg

Experimental group

Description:

apomorphine nasal spray 4 mg

Treatment:

Combination Product: NT-301 4 mg