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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
24
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
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
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
Participants will be randomized to receive single doses of placebo via capsule in a crossover fashion according to a prespecified randomization schedule
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
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
Celerion
Phoenix, Arizona, United States
Clinical Site Partners
Leesburg, Florida, United States
Clinical Site Partners
Winter Park, Florida, United States
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.
Time frame: 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.
Time frame: Part 2- Screening through Day 12
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
Time frame: 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.
PK parameters for plasma NTX-1175: Tmax
Time frame: 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 \[time 0 to the last observed non-zero concentration (t) (AUC0-t), time 0 to Hour 24 (AUC0-24), time 0 extrapolated to infinity (AUC0-inf), percent of AUC0 inf extrapolated (AUC%extrap)\]
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: 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)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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.
Time frame: Part 2- Screening, Day -1, Day 1, Day 3 and Day 5
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