E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10011224 |
E.1.2 | Term | Cough |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Part 1: To evaluate the safety and tolerability of escalating nebulised inhaled doses of NOC 100 (single and 2 consecutive QD doses) in participants with CC.
Part 2: To evaluate the treatment effect of nebulised inhaled doses of NOC 100 as determined by VAS score for cough severity in participants with AC.
To evaluate the safety and tolerability of nebulised inhaled doses of NOC 100 in participants with AC. |
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E.2.2 | Secondary objectives of the trial |
Part 1: To evaluate the treatment effect of escalating nebulised inhaled doses of NOC 100 (single and 2 consecutive QD doses) as determined by awake-coughs per hour in participants with CC.
To evaluate the treatment effect of escalating nebulised inhaled doses of NOC 100 (single and 2 consecutive QD doses) as determined by 24-hour coughs per hour in participants with CC.
To characterise the PK profile of NOC 100 following escalating nebulised inhaled doses (single and 2-consecutive QD doses) in participants with CC.
To identify the dose level and NOC 100 schedule for future development and administration in patients with CC.
Part 2: To evaluate the treatment effect of nebulised inhaled doses of NOC 100 as determined by awake-coughs per hour and 24-hour coughs per hour in participants with AC.
To characterise the PK profile of NOC 100 following nebulised inhaled doses in participants with AC. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Part 1: 1. Male and female participants between the ages of 18 to 80 years, inclusive. 2. Has had CC for ≥ 12 months and a diagnosis of refractory or unexplained CC (Per CHEST chronic cough diagnosis guidelines, Irwin et al, 2018). 3. Chest radiograph or CT thorax within the timeframe supporting the diagnosis of CC, and within the last 60 months, not demonstrating any abnormality considered to be significantly contributing to the CC. 4. If a female of childbearing potential, must be either sexually inactive (abstinent as a lifestyle*) for 28 days prior to the first dosing and throughout the study or using one of the following highly effective birth control methods: a. hormonal oral contraceptives, transdermal patch, or hormone-releasing intrauterine device for at least 3 months prior to the first dosing and with either a physical (e.g., condom, diaphragm, or other) or a chemical (e.g., spermicide) barrier method from the time of screening and throughout the study. b. Depot/implantable hormone (e.g., Depo Provera®, Implanon®) for at least 3 months prior to the first dosing and throughout the study. In addition, female participants of childbearing potential will be advised to remain sexually inactive or to keep the same birth control method for at least 14 days after the last dose of study drug. Females will also be advised not to donate ova during the trial for at least 30 days after the last dose. *abstinence should only be used as a contraceptive method if it is in line with the participants’ usual and preferred lifestyle. Periodic abstinence (calendar, symptothermal, post-ovulation methods) is not an acceptable method of contraception. 5. If a female of non-childbearing potential, must have undergone one of the following sterilisation procedures at least 6 months prior to the first dosing: a. hysteroscopic sterilisation; b. bilateral salpingectomy; c. hysterectomy; d. bilateral oophorectomy or e. or be postmenopausal with amenorrhea for at least 1 year prior to the first dosing and follicle stimulating hormone (FSH) serum levels consistent with postmenopausal status. 6. A non-vasectomised, male participant must agree to use a condom with spermicide or abstain from sexual intercourse during the study until 90 days after the last dosing. (No restrictions are required for a vasectomised male provided his vasectomy has been performed 4 months or more prior to the first dosing. A male who has been vasectomised less than 4 months prior to the first dosing must follow the same restrictions as a non-vasectomised male). 7. If male, must agree not to donate sperm from the first dosing until 90 days after the last dosing. 8. Understands the study procedures in the Informed Consent Form (ICF) and be willing and able to comply with the protocol. Participants must have signed and dated an IRB/IEC approved written ICF including all authorisations required by local law (e.g., collection and handling of personal data, especially health information). The ICF must be obtained before the performance of any protocol related procedures that are not part of the normal standard of care. 9. Aspartate transaminase (AST) and alanine aminotransferase (ALT) <2 x upper limit of normal (ULN); alkaline phosphatase (ALP) and bilirubin ≤1.5 x ULN (isolated bilirubin >1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). 10. Creatinine clearance ≥50 mL/min. 11. Awake-cough frequency of ≥10 per hour (average) at Screening. 12. Score of ≥40 mm on the Cough Severity VAS at Screening.
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E.4 | Principal exclusion criteria |
Part 1: 1. Current smoker or individuals who have given up smoking within the past 6 months prior to screening, or those with >20 pack-year smoking history. 2. Current diagnosis of COPD, bronchiectasis, unexplained pulmonary fibrosis, or asthma. 3. History of concurrent malignancy or recurrence of malignancy in the 2 years prior to the screening visit, participants with adequately treated non-melanomatous skin carcinoma will be permitted. 4. History of recent respiratory tract infection (including SARS-CoV-2 infection) or recent significant change in pulmonary status within 4 weeks of the screening visit. 5. Is currently or has at any time had severe symptoms related to SARS-CoV-2 and required hospitalisation. 6. Is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study. 7. History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the PI or designee. 8. History of any illness that, in the opinion of the PI or designee, might confound the results of the study or poses an additional risk to the participant by their participation in the study. 9. History of recent (within the past 6 months) acute myocardial infarction, acute thromboembolic event, myocarditis, hospitalization for unstable angina or heart failure; history or presence of a clinically important arrhythmia; Wolff-Parkinson-White syndrome or bundle branch block. 10. History or presence of alcohol or drug use disorder, per DSM-5, within the past 2 years prior to screening. 11. History or presence of hypersensitivity to the study drugs or related compounds. 12. Drink alcohol in excess of 21 glasses/units per week for males or 14 glasses/units per week for females, with one unit = 150 mL of wine or 360 mL of beer or 45 mL of 45% alcohol. 13. Current opiate/opioid use in the past 7 days prior to screening, or medical history of opiate/opioid use disorder (OUD). 14. Unable to refrain from the use of: a. Gabapentin, pregabalin, and/or amitryptline or other tricyclics within 4 weeks prior to screening and throughout the study. b. Chronic, systemic corticosteroid use within 4 weeks prior to screening and throughout the study. c. Inhalers including long-acting and short acting beta 2 agonists (LABA, SABA) and ICS within 12 weeks prior to screening and throughout the study. d. Lidocaine or related compounds of any form within 14 days prior to screening and throughout the study. e. Medication or remedies to aid sleeping 14 days prior to screening and throughout the study. f. ACE-inhibitor within 12 weeks prior to screening and throughout the study. g. Antitussives 7 days prior to screening and throughout the study. h. Speech and language therapy for CC within 4 weeks prior to screening and throughout the study. i. Food and beverages containing xanthines/caffeine for 12 hours prior to screening (small amounts of caffeine derived from normal foodstuffs e.g., 250 mL/8 oz./1 cup decaffeinated coffee or other decaffeinated beverage, per day, with the exception of espresso; 45 g/1.5 oz. chocolate bar, per day, would not be considered a deviation to this restriction). j. Food and beverages containing alcohol for 24 h prior to screening. 15. Donation of blood or plasma within 90 days prior to the first dosing. 16. Participation in another clinical study involving an investigational drug within 60 days prior to the first dosing. The 60-day window will be derived from the date of the last blood collection or dosing, whichever is later, in the previous study to Day 1 of the current study. 17. FEV1/FVC <the LLN at screening. 18. Baseline ECG with QTcF interval with heart rate <40bpm, PR ≥ 220msec, QRS ≥120msec, ≥ 460 msec (males) or ≥470 msec (females) or has ECG findings deemed abnormal with clinical significance by the PI or designee at screening. 19. Female participant with a positive pregnancy test at screening or positive pregnancy test at Baseline or lactating. 20. Positive urine drug (not explained by current medical history or medications) or alcohol results at screening or Baseline. 21. Positive cotinine results at screening or Baseline. 22. Positive results at screening for HIV, hepatitis B surface antigen (HBsAg), or HCV (participants successfully treated for HCV may be permitted at the discretion of the PI). 23. Seated BP is less than 90/40 mmHg or greater than 160/95 mmHg at screening. Vital signs may be repeated twice. 24. Seated heart rate is lower than 40 bpm or higher than 99 bpm at screening. Vital signs may be repeated twice. 25. Participant is unable to tolerate the bitter sensitivity solution mouthwash. 26. Received the COVID-19 vaccine (any administration) within 14 days prior to the first dose of NOC-100. Participants scheduled for the COVID-19 vaccine (1st, 2nd, or booster administrations) during the study may be excluded at the discretion of the PI. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Part 1: Incidence of: - TEAEs, - SAEs, - severe AEs, AEs leading to study and/or treatment discontinuation.
Part 2: Relative reduction in VAS score for cough severity Incidence of: - TEAEs, - SAEs, - severe AEs, - AEs leading to study and/or treatment discontinuation
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Please refer to protocol for timepoints. |
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E.5.2 | Secondary end point(s) |
Part 1: Relative reduction in awake cough frequency as determined by VitaloJAK®. Relative reduction in 24-hour cough frequency as determined by VitaloJAK® PK parameters following single doses within each dose level: AUC0 t, AUC0 inf, AUC%extrap, Cmax, Tmax, Kel, t½, CL/F (as appropriate), and Vz/F (as appropriate) NOC-100 dose and regimen for CC
Part 2: Relative reduction in awake-cough and 24 hour cough frequency as determined by VitaloJAK® PK parameters following single doses within each dose level: AUC0 t, AUC0 inf, AUC%extrap, Cmax, Tmax, Kel, t½, CL/F (as appropriate), and Vz/F (as appropriate) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Please refer to protocol for timepoints. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 11 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last scheduled study procedure. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 12 |
E.8.9.1 | In the Member State concerned days | |