Phase 1 Three Part SAD, MAD & Cross-Over Study of ZP-059... | NCT04229303

ID	Type	Description	Link
2019-004031-23	EudraCT Number

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Part 1 - ZP-059 5mg	Experimental	Part 1: administration of single ascending doses (SAD) of ZP-059. Cohort 1: 5mg (1 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.	Drug: Voriconazole inhaled
Part 1 - ZP-059 10mg	Experimental	Part 1: administration of single ascending doses (SAD) of ZP-059. Cohort 2: 10mg (2 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.	Drug: Voriconazole inhaled
Part 1 - ZP-059 20mg	Experimental	Part 1: administration of single ascending doses (SAD) of ZP-059. Cohort 3: 20mg (4 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.	Drug: Voriconazole inhaled
Part 1 - ZP-059 40mg	Experimental	Part 1: administration of single ascending doses (SAD) of ZP-059. Cohort 4: 40mg (8 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.	Drug: Voriconazole inhaled
Part 2 - ZP-059 10mg bid	Experimental	Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Days 1 to 10. Cohort 1: 10mg (2 x 5 mg capsule) ZP-059 twice daily (bid) administered via DPI (RS01 monodose device) for 9 days and once in the morning of Day 10.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Voriconazole inhaled	Drug	Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1. Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10. Part 3 (2-period crossover): eligible subjects received a 4 [20mg BID] inhaled doses of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study. ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Measure	Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAE)	An AE is any untoward medical occurrence in a patient or clinical study subject, temporally associated with the use of IMP, whether or not considered related to the study IMP.	Part 1: screening (Day -28 to -1) to follow-up (8 to 12 days after last dose); part 2: screening (Day -28 to -1) to follow-up (11-17 days after last dose); Part 3: screening (Day -28 to -1) to follow-up (8-12 days after last dose of study drug).

Measure	Description	Time Frame
AUC0-t, AUC0-inf for Voriconazole and N-oxide Voriconazole - Part 1	AUC0-t = Area under the serum concentration time curve from time 0 to time t (hours) (AUC0-t) (AUC0-12 for Part 1) AUC0-inf = Area under the serum concentration time curve from time 0 to infinity	Part 1: at day 1 (pre-dose, at 1.5h-2h-3h-4h-12h post dose).

Eligibility Module

Eligibility Criteria

Inclusion Criteria (part 1):

Female subjects must be either of non-childbearing potential or if of childbearing potential use a highly effective birth control method
Male subjects with female partners of childbearing potential must be vasectomised with documented medical assessment of the surgical success or use highly effective contraception together with their female partner(s)
Subject must agree not to donate semen or ova/oocytes during the study and for 14 days after the last dose of IMP.
BMI ≥ 18.0 and ≤ 35.0 kg/m2 at Screening.
Are willing and able to comply with all aspects of the protocol.
FEV1 ≥80% of the predicted value and FEV1/FVC ratio > 0.70; at screening.
Able to demonstrate the correct inhalation technique for use of delivery device during the study at screening and pre-dose Day 1.

Inclusion Criteria (part 2):

Subjects with mild stable asthma with a documented physician confirmed diagnosis of asthma for at least 3 months prior to screening.
Asthma assessed by investigator as being stable for at least 4 weeks prior to screening and prior to Day 1.
Female subjects must be either of non-childbearing potential or if of childbearing potential use a highly effective birth control method
Male subjects with female partners of childbearing potential must be vasectomised with documented medical assessment of the surgical success or use highly effective contraception together with their female partner(s).
Subject must agree not to donate semen or ova/oocytes during the study and for 14 days after the last dose of IMP.
Body mass index (BMI) ≥ 18.0 and ≤ 35.0 kg/m2 at Screening.
Are willing and able to comply with all aspects of the protocol.
Subject is being treated with short acting beta-agonists alone or in conjunction with low to medium doses of ICS.
Pre-bronchodilator FEV1 ≥70% of the predicted value at screening.
Able to demonstrate the correct inhalation technique for use of delivery device during the study at screening and pre-dose Day 1.

Inclusion Criteria (part 3):

Subjects with mild to moderate stable asthma with a documented physician confirmed diagnosis of asthma for at least 3 months prior to screening.
Asthma assessed by investigator as being stable for at least 4 weeks prior to screening and prior to randomisation.
Female subjects must be either of non-childbearing potential or if of childbearing potential use a highly effective birth control method .
Male subjects with female partners of childbearing potential must be vasectomised with documented medical assessment of the surgical success or use highly effective contraception together with their female partner(s)
Subject must agree not to donate semen or ova/oocytes during the study and for 14 days after the last dose of IMP.
BMI ≥ 18.0 and ≤ 35.0 kg/m2 at Screening.
Are willing and able to comply with all aspects of the protocol.
Subject is being treated with low to medium doses of ICS with or without long-acting beta-agonists.
Pre-bronchodilator FEV1 ≥70% of the predicted value at screening.
Able to demonstrate the correct inhalation technique for use of delivery device during the study at screening and pre-dose Day 1, Treatment Period 1.
Able to produce a sputum sample with a minimum weight of 50 mg at screening.

Exclusion Criteria (part 1):

Subjects who are Chinese or Japanese.
Subjects who have received any IMP in a clinical research study within the previous 3 months prior to Day 1.
Participation in other interventional studies for the duration of the study.
Subjects who are study site employees or immediate family members of a study site or sponsor employee.
History of any drug or alcohol abuse in the past 2 years prior to screening.
Regular alcohol consumption in males >21 units per week and females >14 units per week (1 unit = ½ pint beer, a 25 mL shot of 40% spirit or a 125 mL glass of wine depending on type).
Current tobacco or marijuana smokers and those who have smoked within the last 12 months prior to screening or prior to Day 1.
A confirmed positive urine cotinine test at screening or Day -1.
Current users of e-cigarettes or nicotine replacement products and those who have used these products within the last 12 months prior to screening or prior to Day 1.
Smoking history of >5 pack years at screening.
Females of childbearing potential who are pregnant or lactating, or who plan to become pregnant during the study. A woman is considered of childbearing potential unless she is permanently sterile (hysterectomy, bilateral salpingectomy, bilateral oophorectomy, bilateral tubal occlusion/ligation) or is postmenopausal (had no menses for 12 months without an alternative medical cause).
Female subject with a positive pregnancy test at screening or pre-dose on Day 1.
Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator at screening.
Evidence or history of clinically significant abnormal biochemistry, haematology or urinalysis at screening, as judged by the investigator; the investigator should contact the medical monitor and /or the sponsor if required.
Positive urine drugs of abuse test or alcohol breath test result at screening or Day -1.
History of or currently infected with/carrier of human immunodeficiency virus (HIV).
Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results. Subjects who are HBs antibody positive or HB core antibody positive are not excluded provided the HBsAg result is negative. Subjects who are HCV Ab positive are not excluded if a subsequent HCV RNA test is negative.
Evidence or history of clinically significant cardiovascular, renal, hepatic, endocrine, immunological or autoimmune, dermatological, ophthalmological, chronic respiratory or gastrointestinal disease, neurological or psychiatric disorder, as judged by the investigator.
Subjects with congestive heart failure or a history of congestive heart failure.
12-lead ECGs demonstrating a mean QTcF interval >450 msec for males or QTcF interval >470 msec for females at screening or pre-dose Day 1.
History of severe cough or bronchospasm upon inhalation of any inhalation product.
Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients.
Have had allergies to or hypersensitivity reactions after administration of voriconazole or other antifungal azoles.
Presence or history of clinically significant allergy, including drug allergies, but excluding untreated, mild seasonal allergies, as judged by the investigator. Hay fever is allowed unless it is active.
Major trauma or surgery within the last 3 months prior to screening or prior to Day 1.
Planned or elective surgery or hospitalisations for the duration of the study that may interfere with study logistics or safety.
Donation or loss of more than 400 mL of blood within the previous 3 months prior to screening.
Subjects who are taking, or have taken, any prescribed or over-the-counter drug (other than ≤4 g per day of paracetamol, hormonal contraception or hormone replacement therapy), dietary supplements or CYP3A4 or CYP2C19 inhibitors in the 14 days (or 5 half-lives, whichever is longer) prior to Day 1 and for the duration of the study. Exceptions may apply on a case by case basis, if considered not to interfere with the objectives of the study, as agreed by the Principal Investigator and sponsor's medical monitor.
Subjects who are taking or have taken any herbal remedies or CYP3A4 or CYP2C19 inducers in the 28 days prior to Day 1.
Any use of voriconazole in the 3 months prior to Day 1.
Subjects who have received a live or killed/inactive vaccine in the 14 days prior to Day 1.
Upper respiratory tract infection (excluding otitis media), fever, acute or chronic cough within 14 days of Day 1, or lower respiratory tract infection within the last 4 weeks prior to Day 1.
Recent (within the last 4 weeks prior to Day 1) clinically significant bacterial, viral or fungal infection that required systemic (oral or intravenous) antibiotics, antivirals or antifungals; topical treatments, other than antifungals, are allowed.
Other social, psychiatric, surgical or medical conditions, or screening laboratory abnormalities that may increase subject risk associated with study participation or may interfere with the interpretation of study results and, in the judgement of the investigator would make the subject inappropriate for entry into the study.
Failure to satisfy the investigator of fitness to participate for any reason.

Exclusion Criteria (part 2 and 3):

Subjects who are Chinese or Japanese.
Subjects who have received any IMP in a clinical research study within the previous 3 months prior to Day 1.
Participation in other interventional studies for the duration of the study.
Subjects who are study site employees, or immediate family members of a study site or sponsor employee.
Subjects who have previously received IMP in this study.
History of any drug or alcohol abuse in the past 2 years prior to screening.
Regular alcohol consumption in males >21 units per week and females >14 units per week (1 unit = ½ pint beer, a 25 mL shot of 40% spirit or a 125 mL glass of wine depending on type).
Current tobacco or marijuana smokers and those who have smoked within the last 12 months prior to screening or prior to Day 1.
A confirmed positive urine cotinine test at screening or Day -1.
Current users of e-cigarettes or nicotine replacement products and those who have used these products within the last 12 months prior to screening or prior to Day 1.
Smoking history of >5 pack years at screening.
Females of childbearing potential who are pregnant or lactating, or who plan to become pregnant during the study. A woman is considered of childbearing potential unless she is permanently sterile (hysterectomy, bilateral salpingectomy, bilateral oophorectomy, bilateral tubal occlusion/ligation) or is postmenopausal (had no menses for 12 months without an alternative medical cause).
Female subject with a positive pregnancy test at screening or pre-dose Day 1.
Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator at screening.
Evidence or history of clinically significant abnormal biochemistry, haematology or urinalysis at screening, as judged by the investigator; the investigator should contact the medical monitor and /or the sponsor if required.
Positive urine drugs of abuse test result (unless in the opinion of the investigator this can be explained by the subject's current medications) at screening or Day -1; unexpected positive results may require discussion with sponsor).
Positive alcohol breath test at screening or Day -1.
History of or currently infected with/carrier of HIV.
Positive HBsAg, HCV Ab or HIV results. Subjects who are HBs antibody positive or HB core antibody positive are not excluded provided the HBsAg result is negative. Subjects who are HCV Ab positive are not excluded if a subsequent HCV RNA test is negative.
Evidence or history of clinically significant cardiovascular, renal, hepatic, dermatologic, ophthalmologic or gastrointestinal disease, neurological or psychiatric disorder, as judged by the investigator.
Evidence of history of endocrine, immunological, autoimmune disease that would affect the subject's safety or confound the assessment of study endpoints in the opinion of the investigator.
Current diagnosis of any chronic airways disease other than asthma such as Chronic Obstructive Pulmonary Disease, pulmonary fibrosis, CF, Churg-Strauss syndrome, bronchiectasis.
Evidence of ventricular dysfunction such as congestive cardiac failure (CCF) or a history of CCF assessed at screening and pre-dose Day 1.
12-lead ECG demonstrating a mean QTcF interval >450 msec for males or >470 msec for females at screening or pre-dose Day 1.
Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients.
Have had allergies to or hypersensitivity reactions after administration of voriconazole or other antifungal azoles.
Presence or history of clinically significant allergy, including drug allergies, as judged by the investigator. Hay fever is allowed unless it is active.
Major trauma or surgery within the last 3 months prior to screening or prior to Day 1.
Planned or elective surgery, hospitalisations for the duration of the study that may interfere with study logistics or safety.
Donation or loss of more than 400 mL of blood within the previous 3 months prior to screening.
Subjects who are taking, or have taken, any prescribed or over-the-counter drugs that are CYP3A4 or CYP2C19 inhibitors in the 14 days (or 5 half-lives, whichever is longer) prior to Day 1 and for the duration of the study.
Subjects who are taking or have taken any herbal remedies or CYP3A4 or CYP2C19 inducers in the 28 days prior to Day 1.
Subjects who have received a live or killed/inactive vaccine in the 14 days prior to Day 1.
Presence of hoarseness or oropharyngeal candidiasis at screening or prior to dosing on Day 1.
Any use of voriconazole in the 3 months prior to Day 1.
History of life-threatening asthma, defined as an asthma episode that required intubation and/or was associated with hypercapnia, respiratory arrest and/or hypoxic seizures.
Hospitalisation (including accident and emergency visits) for the treatment of asthma within 3 months prior to screening or prior to Day 1 or have been hospitalised or have attended the accident and emergency for asthma more than twice in the 12 months prior to screening.
Occurrence of asthma exacerbations or respiratory tract infections within 4 weeks prior to screening or prior to Day 1.
Recent (within the last 4 weeks prior to Day 1) clinically significant bacterial, viral or fungal infection that required systemic (oral or intravenous) antibiotics, antivirals or antifungals; topical treatments, other than antifungals, are allowed.
Other social, psychiatric, surgical or medical conditions, or screening laboratory abnormalities that may increase subject risk associated with study participation or may interfere with the interpretation of study results and, in the judgement of the Investigator would make the subject inappropriate for entry into the study.
Failure to satisfy the investigator of fitness to participate for any reason.

Name	Affiliation	Role
Sukh Dave Singh, Prof, MD,	The Medicine Evaluation Unit (MEU) Ltd, Langley building,	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Medicines Evaluation Unit Ltd. (MEU)		Manchester		M239QZ	United Kingdom

PubMed Identifier	Type	Citation	Retractions
39918069	Derived	Caponetti G, Sala F, Cervetti A, Colombo D, Tiberio E, Singh D. Phase I Study of the Safety, Tolerability, and Pharmacokinetics of Inhaled Voriconazole in Healthy Volunteers and Subjects With Stable Asthma. Pharmacol Res Perspect. 2025 Feb;13(1):e70064. doi: 10.1002/prp2.70064.

Arm/Group Information

ID	Title	Description
FG000	Part 1 - ZP-059 5mg	Part 1: administration of single ascending doses (SAD) of ZP-059. Cohort 1: 5mg (1 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1. Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1. Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10. Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study. ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).
FG001	Part 1 - ZP-059 10mg	Part 1: administration of single ascending doses (SAD) of ZP-059. Cohort 2: 10mg (2 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1. Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1. Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10. Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study. ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).
FG002	Part 1 - ZP-059 20mg	Part 1: administration of single ascending doses (SAD) of ZP-059. Cohort 3: 20mg (4 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1. Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1. Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10. Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study. ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).
FG003	Part 1 - ZP-059 40mg	Part 1: administration of single ascending doses (SAD) of ZP-059. Cohort 4: 40mg (8 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1. Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1. Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10. Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study. ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).
FG004	Part 2 - ZP-059 10mg Bid	Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Days 1 to 10. Cohort 1: 10mg (2 x 5 mg capsule) ZP-059 twice daily (bid) administered via DPI (RS01 monodose device) for 9 days and once in the morning of Day 10. Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1. Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10. Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study. ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).
FG005	Part 2 - ZP-059 20mg Bid	Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Day 1 to 10. Cohort 2: 20mg (4 x 5 mg capsule) ZP-059 twice daily (bid) administered via DPI (RS01 monodose device) for 9 days and once in the morning of Day 10. Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1. Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10. Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study. ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).
FG006	Part 2 - ZP-059 40mg qd	Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Day 1 to 10. Cohort 3: 40mg (8 x 5 mg capsule) ZP-059 once daily (qd) d) administered via DPI (RS01 monodose device) on Days 1 to 10. Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1. Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10. Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study. ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).
FG007	Part 3 - ZP-059 / Oral Voriconazole	Crossover treatment period: Single inhaled dose (20 mg) of ZP-059 5mg capsules administered via DPI, and a single dose of oral voriconazole (200 mg Vfend® tablet) on the morning of Day 1 of the respective treatment period with a washout period of at least 96 hours. Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1. Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10. Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study. ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler). oral voriconazole: Part 3 (2-period crossover): eligible subjects received a single dose of oral voriconazole (200mg oral film-coated tablet, Vfend) on the morning of Day 1 according to the crossover scheme of the study.
FG008	Part 3 - Oral Voriconazole / ZP-059	Crossover treatment period: Single dose of oral voriconazole (200 mg Vfend® tablet), and a single inhaled dose (20 mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 of the respective treatment period with a washout period of at least 96 hours. Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1. Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10. Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study. ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler). oral voriconazole: Part 3 (2-period crossover): eligible subjects received a single dose of oral voriconazole (200mg oral film-coated tablet, Vfend) on the morning of Day 1 according to the crossover scheme of the study.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jun 4, 2020	Sep 28, 2021	Prot_000.pdf
SAP	No	Yes	No	Statistical Analysis Plan	Oct 28, 2020	Sep 28, 2021	SAP_001.pdf

ID	Term
D001229	Aspergillosis, Allergic Bronchopulmonary
D001249	Asthma

ID	Term
D055732	Pulmonary Aspergillosis
D001228	Aspergillosis
D009181	Mycoses
D001423	Bacterial Infections and Mycoses

ID	Term
D014230	Triazoles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds