Safety, Tolerability, and Pharmacokinetics of PA9159 Nasal Spray in Healthy Adult Subjects

NCT ID: NCT05170763

Last Updated: 2022-01-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-11-10
• Study Completion Date: 2022-01-05

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.

Conditions

Allergic Rhinitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

PA9159 10 μg single dose and placebo

Ten subjects will be randomly assigned at a 4: 1 ratio to receive either single dose of 10 μg PA9159 or placebo. There will be a one week follow-up period to review all available clinical and laboratory safety data before escalating to next dosing level.

Group Type: EXPERIMENTAL

PA9159 nasal spray solution, 10 μg one day treatment

Intervention Type: DRUG

Single dose of PA9159 (5 μg/nasal spray) is delivered intranasally through a metered-dose mechanical spray pump, one spray each in the left and right nostril.

Placebo, the same intranasal spray solution without PA9159 active ingredient

Intervention Type: DRUG

Placebo is delivered intranasally through a metered-dose mechanical spray pump with the same volume as the corresponding PA9159 dose group

PA9159 20 μg single dose and placebo

Ten subjects will be randomly assigned at a 4: 1 ratio to receive either single dose of 20 μg PA9159 or placebo. There will be a one week follow-up period to review all available clinical and laboratory safety data before escalating to next dosing level.

Group Type: EXPERIMENTAL

PA9159 nasal spray solution, 20 μg one day treatment

Intervention Type: DRUG

Single dose of PA9159 (5 μg/nasal spray) is delivered intranasally through a metered-dose mechanical spray pump, two sprays each in the left and right nostril.

Placebo, the same intranasal spray solution without PA9159 active ingredient

Intervention Type: DRUG

Placebo is delivered intranasally through a metered-dose mechanical spray pump with the same volume as the corresponding PA9159 dose group

PA9159 40 μg single dose and placebo

Ten subjects will be randomly assigned at a 4: 1 ratio to receive either single dose of 40 μg PA9159 or placebo. There will be a one week follow-up period to review all available clinical and laboratory safety data before escalating to next dosing level.

Group Type: EXPERIMENTAL

PA9159 nasal spray solution, 40 μg one day treatment

Intervention Type: DRUG

Single dose of PA9159 (10 μg/nasal spray) is delivered intranasally through a metered-dose mechanical spray pump, two sprays each in the left and right nostril.

Placebo, the same intranasal spray solution without PA9159 active ingredient

Intervention Type: DRUG

Placebo is delivered intranasally through a metered-dose mechanical spray pump with the same volume as the corresponding PA9159 dose group

PA9159 80 μg single dose and placebo

Ten subjects will be randomly assigned at a 4: 1 ratio to receive either single dose of 80 μg PA9159 or placebo. There will be a one week follow-up period to review all available clinical and laboratory safety data.

Group Type: EXPERIMENTAL

PA9159 nasal spray solution, 80 μg one day treatment

Intervention Type: DRUG

Single dose of PA9159 (10 μg/nasal spray) is delivered intranasally through a metered-dose mechanical spray pump, four sprays each in the left and right nostril.

Placebo, the same intranasal spray solution without PA9159 active ingredient

Intervention Type: DRUG

Placebo is delivered intranasally through a metered-dose mechanical spray pump with the same volume as the corresponding PA9159 dose group

PA9159 20 μg repeated doses and placebo

Ten subjects will be randomly assigned at a 4: 1 ratio to receive either 20 μg PA9159 or placebo once a day for 7 days. There will be a one week follow-up period to review all available clinical and laboratory safety data before escalating to next dosing level.

Group Type: EXPERIMENTAL

PA9159 nasal spray solution, 20 μg 7-day treatment

Intervention Type: DRUG

Repeated doses of PA9159 (5 μg/nasal spray) or Placebo is delivered intranasally through a metered-dose mechanical spray pump, two sprays each in the left and right nostril.

Placebo, the same intranasal spray solution without PA9159 active ingredient

Intervention Type: DRUG

Placebo is delivered intranasally through a metered-dose mechanical spray pump with the same volume as the corresponding PA9159 dose group

PA9159 40 μg repeated doses and placebo

Ten subjects will be randomly assigned at a 4: 1 ratio to receive either 40 μg PA9159 or placebo once a day for 7 days. There will be a one week follow-up period to review all available clinical and laboratory safety data.

Group Type: EXPERIMENTAL

PA9159 nasal spray solution, 40 μg 7-day treatment

Intervention Type: DRUG

Repeated doses of PA9159 (10 μg/nasal spray) is delivered intranasally through a metered-dose mechanical spray pump, two sprays each in the left and right nostril.

Placebo, the same intranasal spray solution without PA9159 active ingredient

Intervention Type: DRUG

Placebo is delivered intranasally through a metered-dose mechanical spray pump with the same volume as the corresponding PA9159 dose group

Interventions

PA9159 nasal spray solution, 10 μg one day treatment

Single dose of PA9159 (5 μg/nasal spray) is delivered intranasally through a metered-dose mechanical spray pump, one spray each in the left and right nostril.

Intervention Type: DRUG

PA9159 nasal spray solution, 20 μg one day treatment

Single dose of PA9159 (5 μg/nasal spray) is delivered intranasally through a metered-dose mechanical spray pump, two sprays each in the left and right nostril.

Intervention Type: DRUG

PA9159 nasal spray solution, 40 μg one day treatment

Single dose of PA9159 (10 μg/nasal spray) is delivered intranasally through a metered-dose mechanical spray pump, two sprays each in the left and right nostril.

Intervention Type: DRUG

PA9159 nasal spray solution, 80 μg one day treatment

Single dose of PA9159 (10 μg/nasal spray) is delivered intranasally through a metered-dose mechanical spray pump, four sprays each in the left and right nostril.

Intervention Type: DRUG

PA9159 nasal spray solution, 20 μg 7-day treatment

Repeated doses of PA9159 (5 μg/nasal spray) or Placebo is delivered intranasally through a metered-dose mechanical spray pump, two sprays each in the left and right nostril.

Intervention Type: DRUG

PA9159 nasal spray solution, 40 μg 7-day treatment

Repeated doses of PA9159 (10 μg/nasal spray) is delivered intranasally through a metered-dose mechanical spray pump, two sprays each in the left and right nostril.

Intervention Type: DRUG

Placebo, the same intranasal spray solution without PA9159 active ingredient

Placebo is delivered intranasally through a metered-dose mechanical spray pump with the same volume as the corresponding PA9159 dose group

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Anhui Palo Alto Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Luo Zhang

Role: PRINCIPAL_INVESTIGATOR

Beijing Tongren Hospital

Locations

Beijing TongRen Hospital

Beijing, Beijing Municipality, China

Countries

China

Other Identifiers

PA9159-101

Identifier Type: -

Identifier Source: org_study_id