Placebo-controlled, Single and Multiple Dose Study in Healthy Volunteers and Refractory Chronic Cough Patients to Assess the Safety, Tolerability, and Pharmacokinetics of Two Formulations of NTX-1175

NCT05628740 | Completed Phase 1 FDA Drug

• 1 other identifier: NOC110-C-102
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 3

Brief Summary

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).

Conditions

Refractory Chronic Cough

Outcome Measures

Primary Outcomes (2)

• 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

Secondary Outcomes (18)

• 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.

  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.

  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.

  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.

  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.

  Part 1- Day 1, Day 5, Day 9, Day 13 and Day 17

Study Arms (8)

Part 1-Period 1-Treatment A

EXPERIMENTAL

3 mg NOC-100 (via nebulizer)

Drug: 3 mg NOC-100 (via nebulizer)

Part 1-Periods 2 through 4 -Treatment B

PLACEBO COMPARATOR

1 mg NOC-110 DPI (1 capsule)

Drug: 1 mg NOC-110 (via DPI) [1x 1 mg capsule]

Part 1-Periods 2 through 4 - Treatment C

PLACEBO COMPARATOR

3mg NOC-110 DPI (1 capsule)

Drug: 3 mg NOC-110 (via DPI)

Part 1-Periods 2 through 4- Placebo

PLACEBO COMPARATOR

Placebo (1 capsule)

Drug: Placebo (via DPI)

Part 1-Period 5- Treatment D

PLACEBO COMPARATOR

6mg NOC-110 DPI (2 capsules)

Drug: 6 mg NOC-110 (via DPI)

Part 1-Period 5- Placebo

PLACEBO COMPARATOR

Placebo (2 capsules)

Drug: Placebo (via DPI) [2x Placebo capsules]

Part 2- Active

PLACEBO COMPARATOR

6mg NOC-110 DPI (2 capsules)

Drug: 6 mg NOC-110 (via DPI)

Part 2- Placebo

PLACEBO COMPARATOR

Placebo DPI (2 capsules)

Drug: Placebo (via DPI) [2x Placebo capsules]

Interventions

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

Part 1-Period 1-Treatment A

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

Part 1-Periods 2 through 4 -Treatment B

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

Part 1-Periods 2 through 4 - Treatment C

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

Part 1-Periods 2 through 4- Placebo

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

Part 1-Period 5- Treatment D; Part 2- Active

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

Part 1-Period 5- Placebo; Part 2- Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must meet all of the following criteria to be eligible for participation in the study:
• Male or female participants between the ages of 18 to 65 years, inclusive, at the time of screening (Part 1) and between the ages of 18 to 85 years, inclusive, at the time of screening (Part 2).
• Has had rCC diagnosis for ≥ 12 months (Part 2) prior to screening.
• Awake-cough frequency of ≥20 per hour (average) at Screening (Part 2).
• Score of ≥40 mm on the Cough Severity Visual Analog Scale (VAS) at Screening (Part 2).
• Chest radiograph or CT thorax within the last 60 months not demonstrating any abnormality considered to be significantly contributing to the rCC. (Part 2)
• Body mass index (BMI) ≥19.0 and ≤32.0 kg/m2, inclusive, at Screening.
• Aspartate aminotransferase (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%).
• Creatinine clearance ≥50 mL/min.
• Must be fully SARS-CoV-2 vaccinated.
• Must be SARS-CoV-2 negative via rapid antigen testing or polymerase chain reaction (PCR) test at Screening and PCR at Check-in Day -1.
• In the Investigator's opinion, has no clinically significant disease and/or clinically significant abnormal laboratory values as determined by the Investigator based on medical history, physical examination, or laboratory evaluations conducted at the screening visit or on admission to the clinical research unit.

You may not qualify if:

• 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:
• Gabapentin, pregabalin, and/or amitryptline or other tricyclics within 4 weeks prior to screening and throughout the study (Part 2)
• Chronic, systemic corticosteroid use within 4 weeks prior to screening and throughout the study (Part 2).
• Inhalers including long-acting and short acting beta 2-agonists (LABA and SABA), and inhaled corticosteroids (ICS) within 8 weeks prior to screening and throughout the study.
• Lidocaine or related compounds of any form within 14 days prior to screening and throughout the study (Part 2).
• Medication or remedies to aid sleeping 14 days prior to screening and throughout the study (Part 2).
• Angiotensin-converting enzyme (ACE)-inhibitor within 12 weeks prior to screening and throughout the study (Part 2).
• Antitussives 7 days prior to screening and throughout the study (Part 2).
• Speech and language therapy for rCC within 4 weeks prior to screening and throughout the study (Part 2).

Sponsors & Collaborators

• Nocion Therapeutics: lead

Study Sites (3)

Celerion

Phoenix, Arizona, 85283, United States

Location

Clinical Site Partners

Leesburg, Florida, 32789, United States

Location

Clinical Site Partners

Winter Park, Florida, 34748, United States

Location

MeSH Terms

Conditions

Chronic Cough

Condition Hierarchy (Ancestors)

Cough; Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Christopher Silber, MD

  Nocion Therapeutics, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: November 2, 2022
• First Posted: November 29, 2022
• Study Start: February 7, 2022
• Primary Completion: October 25, 2022
• Study Completion: October 25, 2022
• Last Updated: March 30, 2023

Record last verified: 2022-11

Locations

US (3)