Staccato® Granisetron Single Dose PK
- Conditions
- Healthy
- Interventions
- Combination Product: 0.5mg AZ-010; placeboCombination Product: 3mg AZ-010Combination Product: AZ-010 1mgCombination Product: 1mg AZ-010Other: PlaceboDrug: IV Granisetron 1mg
- Registration Number
- NCT04200092
- Lead Sponsor
- Alexza Pharmaceuticals, Inc.
- Brief Summary
This study was conducted in 2 parts in separate treatment groups of healthy volunteers. Part A of the study was double-blind, randomized, and placebo-controlled; Part B is open label.
The primary objectives for each part were as follows:
Part A:
1. To examine the tolerability and safety of single ascending doses up to 3 mg of AZ-010 (Staccato Granisetron) in healthy volunteers
2. To characterize the pharmacokinetics (PK) of single ascending doses up to 3 mg of AZ-010 in healthy volunteers
Part B:
1. To compare the PK and safety of a single dose of 1 mg of AZ-010 with that of 1 mg granisetron hydrochloride intravenous (IV) injection in healthy volunteers.
The 2 parts to the study were performed sequentially.
- Detailed Description
Part A assessed single ascending orally inhaled doses of AZ-010 in a double-blind, placebo controlled design. The planned AZ-010 doses to be studied were 0.5 mg, 1 mg, and 3 mg delivered from 1 device each.
There were 3 cohorts of at least 8 subjects each, with at least 2 males and 2 females in each cohort. Each subject received a single dose of AZ-010, or matching Staccato® placebo; 6 subjects received AZ-010 and 2 subjects received Staccato® placebo per cohort.
Upon completion of each cohort, a review of the in-clinic safety and tolerability data was performed by the Principal Investigator (PI), Medical Monitor, and an independent data safety monitoring board (DSMB) to determine if there were adequate safety and tolerability data to support escalation to the next dose up to 3 mg.
Safety was evaluated by the PI, Medical Monitor, and DSMB upon completion of Part A and prior to start of Part B. PK data were analyzed and assessed through blood samples obtained for Parts A and B.
Part B Approximately 12 healthy volunteers were enrolled in this 2-period, 2-treatment open-label crossover design study assessing the PK profiles of AZ-010 (1 mg) and IV granisetron (1 mg).
Eligible consenting subjects were randomized to 1 of 2 treatment sequences, with a total of 12 subjects (6 subjects in each sequence, with at least 2 males and 2 females in each sequence).
Treatment periods were separated by at least a 3-day washout between doses.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 36
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part A: Cohort 1 0.5mg AZ-010; placebo A single oral dose of 0.5 mg AZ-010 (Staccato Granisetron) administered to 8 subjects, with at least 2 males and 2 females. Each subject received a single dose of 0.5 mg AZ-010, or matching Staccato® placebo; 6 subjects received AZ-010 and 2 subjects received Staccato® placebo. Upon completion of the cohort, a review of the in-clinic safety and tolerability data was performed by the PI, Medical Monitor, and an independent data safety monitoring board (DSMB) to determine if there were adequate safety and tolerability data to support escalation to the next dose. Safety was evaluated by the PI, Medical Monitor, and DSMB upon completion of Part A and prior to start of Part B. Each subject participated for up to 4 weeks, depending upon the timing of screening. Subjects were confined to the clinic for 4 days (3 nights). A follow-up phone call was conducted, approximately 7 days after the subject left the CRU. Part A: Cohort 3 3mg AZ-010 A single oral dose of 3 mg AZ-010 (Staccato Granisetron) administered to 8 subjects, with at least 2 males and 2 females. Each subject received a single dose of 3 mg AZ-010, or matching Staccato® placebo; 6 subjects received AZ-010 and 2 subjects received Staccato® placebo. Upon completion of the cohort, a review of the in-clinic safety and tolerability data was performed by the PI, Medical Monitor, and an independent data safety monitoring board (DSMB) to determine if there were adequate safety and tolerability data to support escalation to the next dose. The single daily dose did not exceed 3 mg. Safety was evaluated by the PI, Medical Monitor, and DSMB upon completion of Part A and prior to start of Part B. Each subject participated for up to 4 weeks, depending upon the timing of screening. Subjects were confined to the clinic for 4 days (3 nights). A follow-up phone call was conducted, approximately 7 days after the subject left the CRU. Part B: Sequence 1 AZ-010 1mg A single inhalation dose of 1 mg AZ-010, followed by IV injection granisetron 1mg, 2-period, a 2-treatment open-label crossover design. Participants were randomized in a 1:1 ratio to 1 of 2 sequences. Period 1 began with the inhalation dose of AZ-010 1mg and after a three-day washout participants were crossed over to the other sequence for Period 2 with the treatment of IV injection granisetron 1 mg dose. There was a total of 12 subjects (6 subjects in each sequence, with at least 2 males and 2 females in each sequence). Sequence 1 participants crossed over to Sequence 2 after washout. Part A: Cohort 2 1mg AZ-010 A single oral dose of 1 mg AZ-010 (Staccato Granisetron) administered to 8 subjects, with at least 2 males and 2 females. Each subject received a single dose of 1 mg AZ-010, or matching Staccato® placebo; 6 subjects received AZ-010 and 2 subjects received Staccato® placebo. Upon completion of the cohort, a review of the in-clinic safety and tolerability data was performed by the PI, Medical Monitor, and an independent data safety monitoring board (DSMB) to determine if there were adequate safety and tolerability data to support escalation to the next dose. The single daily dose did not exceed 3 mg. Safety was evaluated by the PI, Medical Monitor, and DSMB upon completion of Part A and prior to start of Part B. Each subject participated for up to 4 weeks, depending upon the timing of screening. Subjects were confined to the clinic for 4 days (3 nights). A follow-up phone call was conducted, approximately 7 days after the subject left the CRU. Part B: Sequence 1 IV Granisetron 1mg A single inhalation dose of 1 mg AZ-010, followed by IV injection granisetron 1mg, 2-period, a 2-treatment open-label crossover design. Participants were randomized in a 1:1 ratio to 1 of 2 sequences. Period 1 began with the inhalation dose of AZ-010 1mg and after a three-day washout participants were crossed over to the other sequence for Period 2 with the treatment of IV injection granisetron 1 mg dose. There was a total of 12 subjects (6 subjects in each sequence, with at least 2 males and 2 females in each sequence). Sequence 1 participants crossed over to Sequence 2 after washout. Part B: Sequence 2 AZ-010 1mg Treatment of 1 mg (IV) granisetron followed by a single inhalation dose of AZ-010 1mg, a 2-period, 2-treatment open-label crossover design. Part B Sequence 2 participants began with Period 1 treatment of IV injection granisetron 1 mg dose and after a three-day washout participants were crossed over to the other sequence for Period 2 with the inhalation dose of AZ-010 1mg. There was a total of12 subjects (6 subjects in each sequence, with at least 2 males and 2 females in each sequence). Sequence 2 participants crossed over to Sequence 1 after washout. Part B: Sequence 2 IV Granisetron 1mg Treatment of 1 mg (IV) granisetron followed by a single inhalation dose of AZ-010 1mg, a 2-period, 2-treatment open-label crossover design. Part B Sequence 2 participants began with Period 1 treatment of IV injection granisetron 1 mg dose and after a three-day washout participants were crossed over to the other sequence for Period 2 with the inhalation dose of AZ-010 1mg. There was a total of12 subjects (6 subjects in each sequence, with at least 2 males and 2 females in each sequence). Sequence 2 participants crossed over to Sequence 1 after washout. Pooled Placebo, Cohort 1, 2, 3 Part A Placebo Participants in Part A, Cohorts 1, 2, and 3, double-blind, randomized, and placebo-controlled study who received placebo.
- Primary Outcome Measures
Name Time Method Measurement of Granisetron Time to Maximum Exposure in Plasma 3 days Tmax
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]). 3 days Number of Subjects with Adverse Events as a Measure of Safety and Tolerability
Measurement of Granisetron Exposure in Plasma 3 days AUC (area under the curve)
Measurement of Granisetron Maximum Exposure in Plasma 3 days Cmax
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
Celerion
🇺🇸Tempe, Arizona, United States