Clinical trial NCT05170763: Safety, Tolerability, and Pharmacokinetics of PA9159 Nasal Spray in Healthy Adult Subjects
Official title: A Randomized, Double-blind, Placebo-controlled, Dose Escalation Study to Assess the Safety, Tolerability, Pharmacokinetics of Single Dose and 7-day Repeat Doses of PA9159 Nasal Spray in Healthy Chinese Adult
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Allergic Rhinitis
Lead sponsor: Anhui Palo Alto Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2021-12-28
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Arm 1-4, the treatment is given once for one day, with escalation doses of 10 μg, 20 μg, 40 μg, 80 μg. Arm 5-6, PA9159 at the escalation dose of 20 μg and 40 μg is given once a day for 7 days. 10 health subjects will be enrolled for each dose group, randomized proportionally at 4:1 ratio to receive either the investigational product PA9159 or placebo nasal spray, with a total of 60 subjects.
Primary purpose: TREATMENT

Brief summary: PA9159 is a highly potent novel corticosteroid. The purpose of this study is to exam the safety, tolerability, and pharmacokinetics of single and repeat dosing of intranasal PA9159, to establish maximum tolerated dose in healthy chinese adult

Detailed description: This is a randomized, double-blind, placebo-controlled dose escalation phase 1 trial, including single dose and 7-day repeat doses of PA9159 nasal spray. In the first part of the study, the treatment is given once for one day, with escalation doses of 10 μg, 20 μg, 40 μg, 80 μg. In the second part of the study, PA9159 at the escalation dose of 20 μg and 40 μg is given once a day for 7 days. 10 health subjects will be enrolled for each dose group, randomized proportionally at 4:1 ratio to receive either the investigational product PA9159 or placebo nasal spray, with a total of 60 subjects for this two-part study. Subjects will be evaluated for the safety, tolerability and pharmacokinetics of PA9159 intranasal spray.

Eligibility criteria: Inclusion Criteria:

* Male and female subjects aged 18 to 65 years (including upper and lower limits);
* Male body weight ≥ 50 kg, female weight ≥ 45 kg, body mass index (BMI) between 19 and 28 kg/m2 (including cut-off values);
* Voluntary participation and signing of informed consent.

Exclusion Criteria:

* Those with a history or current history of serious diseases such as respiratory, cardiovascular, digestive, endocrine, hematological, immune, psychiatric, neurological, and otologic diseases, with special attention to a history of recurrent (defined as \> 1) or disseminated herpes zoster, history of recurrent infections, tuberculosis infection, glaucoma and cataract; Suffering from acute, chronic or local infectious diseases (e.g., eye, nose infection, etc.);
* Those who are allergic to the study drug or any component of the study drug (refer to the susceptibility of the body to allergic reactions, or to a variety of food, drugs, or environmental substances);
* Any past or current medical history that may affect the safety of the study in the body, especially any nasal disorder affecting drug absorption: a) History of long-term nasal congestion, rhinorrhea, nasal pruritus, headache, epistaxis, etc.; b) asthma, aspirin stress response, chronic respiratory disease, etc.; c) History of nasal surgery, trauma, allergic rhinitis, chronic rhinitis, sinusitis, severe deviation of nasal septum, etc., and the researchers believe that it is still clinically significant;
* Abnormal and clinically significant vital signs, physical examination, nasal examination, laboratory tests (hematology, blood chemistry, urinalysis, coagulation function, serum cortisol), ECG, etc., during screening;
* Positive test results and have clinical significance for human immunodeficiency virus HIV-P24 antigen/antibody, hepatitis C virus (HCV) antibody, treponema pallidum (TP), or hepatitis B five items (hepatitis B surface antigen, hepatitis B surface antibody, hepatitis B e antigen, hepatitis B e antibody, and hepatitis B core antibody);
* Regular drinkers within 6 months prior to screening,That is, drink more than 14 units of alcohol per week (1 unit = 360 mL of beer containing 5% alcohol or 45 mL of spirits with 40% alcohol or 150 mL of wine with 12% alcohol content) or who have a positive alcohol breath test at screening or who cannot stop alcohol intake during the study;
* Smoking more than 5 cigarettes per day on average within 3 months prior to screening, or unable to discontinue the use of any tobacco products during the trial;
* History of drug abuse, history of drug abuse, or positive urine screening for drug abuse (including morphine, methamphetamine, ketamine, dimethyldioxymethamphetamine, tetrahydrocannabinol acid);
* Those who have taken any drugs (prescription drugs, over-the-counter drugs, Chinese herbal medicines, vaccines) or health products within 2 weeks prior to screening and during screening;
* Those who have used glucocorticoid-containing preparations or any drugs that affect CYP3A4 enzyme activity (e.g., ritonavir or ketoconazole, etc.) within 30 days prior to screening and during screening;
* Consumption of beverages or foods containing grapefruit, dragon fruit, mango, grapefruit, pomegranate, papaya, carambola within 14 days prior to screening and during screening, or who do not agree to stop eating the above-mentioned diet during the study;
* Consumption of any caffeine- and xanthine-rich food or beverages (coffee, tea, cola, chocolate, seafood, animal liver, etc.) within 48 hours prior to the first dose of study drug, or who do not agree to stop eating these diets during the study;
* It cannot be guaranteed that effective contraceptive measures or fertility planners or sperm or egg donors are taken during the trial and for at least 1 year after the last dose;
* Donation or massive blood loss (≥ 300 mL, except during female physiology) or use of blood products or transfusions within 90 days prior to screening and during screening;
* Participating in other clinical investigators or subjects participating in other clinical trials within 90 days prior to screening for less than 7 days;
* Major surgery (as judged by the investigator based on past medical history data), major trauma, or planned surgery during the study within 6 months prior to screening;
* Difficulty in venous blood collection, or a known history of multiple needle sickness and blood sickness;
* Women with a positive pregnancy test or breastfeeding;
* Other conditions that, in the opinion of the investigator, are not suitable for participation in the study or the subject is unable to participate in the study due to his/her own reasons.

Primary outcomes:
measure: Number of subjects experiencing adverse events (AEs)
timeFrame: up to 7 days after last nasal spray treatment
measure: Number of subjects having abnormal hematology laboratory parameters
timeFrame: within 24 hours after last nasal spray treatment
measure: Number of subjects with abnormal clinical chemistry parameters
timeFrame: within 24 hours after last nasal spray treatment
measure: Number of subjects with abnormal values for urinalysis
timeFrame: within 24 hours after last nasal spray treatment
measure: Body temperature
timeFrame: up to 24 hours after last nasal spray treatment
measure: Systolic and diastolic blood pressure
timeFrame: up to 24 hours after last nasal spray treatment
measure: Pulse rate
timeFrame: up to 24 hours after last nasal spray treatment
measure: ECG parameter-QTc interval
timeFrame: up to 24 hours after last nasal spray treatment
measure: ECG parameter-PR interval
timeFrame: up to 24 hours after last nasal spray treatment
measure: ECG parameter-QRS duration
timeFrame: up to 24 hours after last nasal spray treatment
measure: Numbers of subjects experiencing local nasal/throat irritation symptoms
timeFrame: up to 24 hours after nasal spray treatment
measure: Numbers of subjects showing signs of local reactions
timeFrame: up to 24 hours after nasal spray treatment
Secondary outcomes:
measure: Serum cortisol levels
timeFrame: From pre-dose until 24 hours post-dose
measure: Pharmacokinetics of single dose and repeat doses of Nasal Spray PA9159-Cmax
timeFrame: Pre-dose, and post-dose (day 1 for single dose subjects, day 1 and day 7 for repeat doses subjects) 10, 20, 30 minutes, 1, 1.5, 2, 3 , 4, 6, 8,12, 24 hours, and for repeat doses subjects, also 30 minutes pre-dose on day 4, day 5 and day 6
measure: Pharmacokinetics of single dose and repeat doses of Nasal Spray PA9159-Tmax
timeFrame: Pre-dose, and post-dose (day 1 for single dose subjects, day 1 and day 7 for repeat doses subjects) 10, 20, 30 minutes, 1, 1.5, 2, 3 , 4, 6, 8,12, 24 hours, and for repeat doses subjects, also 30 minutes pre-dose on day 4, day 5 and day 6
measure: Pharmacokinetics of single dose and repeat doses of Nasal Spray PA9159-AUC
timeFrame: Pre-dose, and post-dose (day 1 for single dose subjects, day 1 and day 7 for repeat doses subjects) 10, 20, 30 minutes, 1, 1.5, 2, 3 , 4, 6, 8,12, 24 hours, and for repeat doses subjects, also 30 minutes pre-dose on day 4, day 5 and day 6
measure: Pharmacokinetics of single dose and repeat doses of Nasal Spray PA9159-T1/2
timeFrame: Pre-dose, and post-dose (day 1 for single dose subjects, day 1 and day 7 for repeat doses subjects) 10, 20, 30 minutes, 1, 1.5, 2, 3 , 4, 6, 8,12, 24 hours, and for repeat doses subjects, also 30 minutes pre-dose on day 4, day 5 and day 6
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing TongRen Hospital
state: Beijing
Study officials:
affiliation: Beijing Tongren Hospital
name: Luo Zhang
role: PRINCIPAL_INVESTIGATOR
References: