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Part 1 will evaluate the safety, tolerability and PK of single doses of three dose levels of NTX-1175 drug substance administered by dry powder inhaler (NOC-110) compared to a single dose reference nebulizer (NOC-100) treatment in healthy participants.
Part 2 will evaluate the safety, tolerability and PK of multiple doses of NTX-1175 drug substance administered by dry powder inhaler (NOC-110) to participants with refractory chronic cough. Part 2 will also evaluate the treatment effect of multiple doses of one dose level of NTX-1175 drug substance administered by dry powder inhaler (NOC-110).
Part 1 is a randomized, double-blinded 3 period crossover and 1 period parallel study of single dose administration of NOC-110 via dry powder inhaler, preceded by a reference period of NOC-100 administered via nebulizer. A total of 12 healthy participants will be enrolled to ensure that 9 participants complete this part of study.
Part 2 is a randomized, double-blinded, placebo-controlled, multiple-dose, parallel design study in patients with refractory chronic cough. A total of 12 participants will be enrolled to ensure that 8 participants complete this part of study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1-Period 1-Treatment A | Experimental | 3 mg NOC-100 (via nebulizer) |
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| Part 1-Periods 2 through 4 -Treatment B | Placebo Comparator | 1 mg NOC-110 DPI (1 capsule) |
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| Part 1-Periods 2 through 4 - Treatment C | Placebo Comparator | 3mg NOC-110 DPI (1 capsule) |
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| Part 1-Periods 2 through 4- Placebo | Placebo Comparator | Placebo (1 capsule) |
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| Part 1-Period 5- Treatment D | Placebo Comparator | 6mg NOC-110 DPI (2 capsules) |
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| Part 1-Period 5- Placebo | Placebo Comparator | Placebo (2 capsules) |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 3 mg NOC-100 (via nebulizer) | Drug | Participants determined to be eligible for Part 1 of the study will be enrolled and will be assigned to receive a single dose of the reference nebulizer treatment of NOC 100 at 3 mg (Treatment A) in Period 1 |
| Measure | Description | Time Frame |
|---|---|---|
| Number and severity of Treatment Emergent Adverse Events (TEAEs) following single doses of NOC-110 or placebo administered with a DPI | To evaluate the safety and tolerability of single doses of three dose levels of NTX-1175 drug substance administered by DPI (Drug Product NOC-110) compared to a single dose reference nebulizer treatment (Drug Product NOC-100) in healthy participants, number and severity of TEAEs following single doses of NOC-110 or placebo administered with a DPI compared to a reference period administration of NOC 100 via a nebulizer in healthy adult participants will be reported. | Part 1- Screening through Day 23 |
| Number and severity of TEAE following repeat doses of NOC 110 compared to placebo in participants with chronic cough. | To evaluate the safety and tolerability of multiple doses of NOC-110 administered by DPI to participants with refractory chronic cough (rCC), number and severity of TEAE following repeat doses of NOC 110 compared to placebo in participants with chronic cough will be reported. | Part 2- Screening through Day 12 |
| Measure | Description | Time Frame |
|---|---|---|
| Peak plasma concentration (Cmax) of single doses of three dose levels of NOC-110 administered by DPI compared to a single dose reference nebulizer treatment (NOC-100) in healthy participants. | PK parameters for plasma NTX-1175: Cmax | Part 1- Day 1, Day 5, Day 9, Day 13 and Day 17 |
| The time to reach maximum observed concentration (Tmax) of single doses of three dose levels of NOC-110 administered by DPI compared to a single dose reference nebulizer treatment (NOC-100) in healthy participants. |
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Inclusion Criteria:
Participants must meet all of the following criteria to be eligible for participation in the study:
Exclusion Criteria:
Participants who meet any one of the following criteria will be deemed ineligible for participation in the study:
Is found to have positive test for SARS-CoV-2 at Screening or Check-in Day -1, whether or not this was accompanied by the clinical symptoms of COVID-19.
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 (Part 2)
Current diagnosis of chronic obstructive pulmonary disease (COPD), bronchiectasis, unexplained pulmonary fibrosis, or asthma (Part 2).
History or presence of alcohol or drug use disorder, per Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5), within the past 2 years prior to screening.
Current opiate/opioid use in the past 7 days prior to screening, or medical history of opiate/opioid use disorder.
Unable to refrain from the use of:
History or presence of cardiac dysfunction including arrhythmia, bundle branch block; Wolff Parkinson White syndrome, recent thromboembolic event, prolonged PR (≥220 msec), QRS (≥120 msec), QTcF interval (≥450 msec [males] or ≥470 msec [females]) or has ECG findings deemed abnormal with clinical significance by the Investigator or designee at Screening.
Positive results at Screening for HIV, HBsAg, or HCV (participants successfully treated for HCV may be permitted at the discretion of the Investigator).
Supine blood pressure is less than 90/40 mmHg or greater than 140/90 mmHg (Part 1), or greater than 160/95 mmHg (Part 2) at Screening. Vital signs may be repeated twice.
Supine heart rate is lower than 40 beats per minute (bpm) or higher than 99 bpm at Screening. Vital signs may be repeated twice.
History of asthma or COPD (Part 1).
Forced expiratory volume in 1 second/ forced vital capacity (FEV1/FVC) < lower limit of normal (LLN) per Global Lung Health Initiative normative dataset at Screening.
Had symptoms of any significant acute illness, including symptoms of COVID-19 within 30 days before the start of the study (time of first dose), as determined by the Investigator.
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| Name | Affiliation | Role |
|---|---|---|
| Christopher Silber, MD | Nocion Therapeutics, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Celerion | Phoenix | Arizona | 85283 | United States | ||
| Clinical Site Partners |
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Part 1: randomized, double-blind, placebo-controlled, 3-period crossover, and 1-period parallel study.
Part 2: randomized, double-blind, placebo-controlled, multiple-dose, parallel-design.
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A computerized randomization scheme for Part 1 and Part 2 will be created by a blinded study statistician and it shall be considered blinded per the following: The randomization is available only to the unblinded Clinic pharmacy staff who are preparing the study drug and who will not be involved in any other aspect of the study including administration of the study drug. The randomization scheme will not be made available to the Sponsor, study participants, or members of the staff responsible for the monitoring and evaluation of safety assessments.
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| Part 2- Active | Placebo Comparator | 6mg NOC-110 DPI (2 capsules) |
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| Part 2- Placebo | Placebo Comparator | Placebo DPI (2 capsules) |
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| 1 mg NOC-110 (via DPI) [1x 1 mg capsule] | Drug | Participants will be randomized to receive single doses of 1 mg NOC-110 (via DPI) in a crossover fashion according to a prespecified randomization schedule |
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| 3 mg NOC-110 (via DPI) | Drug | Participants will be randomized to receive single doses of 3 mg NOC-110 (via DPI) in a crossover fashion according to a prespecified randomization schedule |
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| Placebo (via DPI) | Drug | Participants will be randomized to receive single doses of placebo via capsule in a crossover fashion according to a prespecified randomization schedule |
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| 6 mg NOC-110 (via DPI) | Drug | Participants will be randomized to receive single doses of 6 mg NOC-110 via DPI in a parallel fashion according to a prespecified randomization schedule |
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| Placebo (via DPI) [2x Placebo capsules] | Drug | Participants will be randomized to receive single doses of Placebo (via DPI) [2x Placebo capsules] in a parallel fashion according to a prespecified randomization schedule |
|
PK parameters for plasma NTX-1175: Tmax |
| Part 1- Day 1, Day 5, Day 9, Day 13 and Day 17 |
| The area under the concentration-time (AUC) curve of single doses of three dose levels of NOC-110 compared to a single dose reference nebulizer treatment in healthy participants. | PK parameters for plasma NTX-1175: AUC [time 0 to the last observed non-zero concentration (t) (AUC0-t), time 0 to Hour 24 (AUC0-24), time 0 extrapolated to infinity (AUC0-inf), percent of AUC0 inf extrapolated (AUC%extrap)] | Part 1- Day 1, Day 5, Day 9, Day 13 and Day 17 |
| The time of the last measurable concentration (Tlast) of single doses of three dose levels of NOC-110 administered by DPI compared to a single dose reference nebulizer treatment (NOC-100) in healthy participants. | PK parameters for plasma NTX-1175: Tlast | Part 1- Day 1, Day 5, Day 9, Day 13 and Day 17 |
| The apparent terminal elimination half-life (t½) of single doses of three dose levels of NOC-110 administered by DPI compared to a single dose reference nebulizer treatment (NOC-100) in healthy participants. | PK parameters for plasma NTX-1175: t½ | Part 1- Day 1, Day 5, Day 9, Day 13 and Day 17 |
| The apparent terminal elimination rate constant (Kel) of single doses of three dose levels of NOC-110 administered by DPI compared to a single dose reference nebulizer treatment (NOC-100) in healthy participants. | PK parameters for plasma NTX-1175: Kel | Part 1- Day 1, Day 5, Day 9, Day 13 and Day 17 |
| The Cmax of multiple doses of NOC 110 administered by DPI to participants with rCC. | PK parameters for plasma NTX-1175: Cmax and maximum observed concentration at steady-state (Cmax, ss) | Part 2- Day 1, Day 5 |
| The Tmax of multiple doses of NOC 110 administered by DPI to participants with rCC. | PK parameters for plasma NTX-1175: Tmax, time to reach Cmax,ss (Tmax,ss) | Part 2- Day 1, Day 5 |
| The AUC of multiple doses of NOC 110 administered by DPI to participants with rCC. | PK parameters for plasma NTX-1175: AUC0-t AUC0-inf AUC%extrap | Part 2- Day 1, Day 5 |
| The Tlast of multiple doses of NOC 110 administered by DPI to participants with rCC. | PK parameters for plasma NTX-1175: Tlast | Part 2- Day 1, Day 5 |
| The t½ of multiple doses of NOC 110 administered by DPI to participants with rCC. | PK parameters for plasma NTX-1175: t½ | Part 2- Day 1, Day 5 |
| The Kel multiple doses of NOC 110 administered by DPI to participants with rCC. | PK parameters for plasma NTX-1175: Kel | Part 2- Day 1, Day 5 |
| The concentration observed at the end of the dosing interval (Ctrough) of multiple doses of NOC 110 administered by DPI to participants with rCC. | PK parameters for plasma NTX-1175: Ctrough | Part 2- Days 2 to 4 |
| The minimum observed non zero concentration between dose time and dose time + dosing interval (tau) (min,ss,) of multiple doses of NOC 110 administered by DPI to participants with rCC. | PK parameters for plasma NTX-1175: Cmin,ss | Part 2- Day 5 |
| The area under the concentration-time curve during a dosing interval (tau), at steady state (AUCtau) of multiple doses of NOC 110 administered by DPI to participants with rCC. | PK parameters for plasma NTX-1175: AUCtau | Part 2- Day 5 |
| The average concentration during a dosing interval, at steady state (Cavg,ss) of multiple doses of NOC 110 administered by DPI to participants with rCC. | PK parameters for plasma NTX-1175: Cavg,ss | Part 2- Day 5 |
| The accumulation (R) of multiple doses of NOC 110 administered by DPI to participants with rCC. | PK parameters for plasma NTX-1175: R | Part 2- Day 5 |
| Awake-coughs per hour in participants with rCC | The treatment effect of multiple doses of one dose level of NOC-110 administered by DPI, as determined by awake-coughs per hour in participants with rCC. | Part 2- Screening, Day -1, Day 1, Day 3 and Day 5 |
| Leesburg |
| Florida |
| 32789 |
| United States |
| Clinical Site Partners | Winter Park | Florida | 34748 | United States |
| ID | Term |
|---|---|
| D000096822 | Chronic Cough |
| ID | Term |
|---|---|
| D003371 | Cough |
| D012120 | Respiration Disorders |
| D012140 | Respiratory Tract Diseases |
| D012818 | Signs and Symptoms, Respiratory |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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