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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05351086




Registration number
NCT05351086
Ethics application status
Date submitted
19/04/2022
Date registered
28/04/2022
Date last updated
23/12/2022

Titles & IDs
Public title
A Study to Assess the Safety, Tolerability, and Pharmacokinetics of PUR3100 in Health Adults
Scientific title
A Double Dummy, Double-blind Study to Assess the Safety, Tolerability, and Pharmacokinetics of PUR3100 in Health Adults
Secondary ID [1] 0 0
601-0022
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Healthy 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - PUR3100
Treatment: Drugs - Dihydroergotamine (D.H.E 45)
Other interventions - Matching Placebo for PUR3100
Other interventions - Matching Placebo for D.H.E 45

Experimental: Inhaled placebo and IV D.H.E. 45 1 mg -

Experimental: Inhaled PUR3100 0.5 mg and IV placebo -

Experimental: Inhaled PUR3100 1.0 mg and IV placebo -

Experimental: Inhaled PUR3100 1.5 mg and IV placebo -


Treatment: Drugs: PUR3100
PUR3100 is an inhalation powder containing DHE, an anti-migraine treatment with broad spectrum agonist activity against 5-hydroxytryptamine (5-HT), dopamine, and adrenergic receptors. PUR3100 is provided as 500 µg dose strength capsules. Each capsule contains the drug substance, DHE mesylate, with mannitol, leucine, and sodium chloride as excipients.

Treatment: Drugs: Dihydroergotamine (D.H.E 45)
D.H.E. 45 is ergotamine hydrogenated in the 9, 10 position as the mesylate salt. It is supplied as a clear, colorless solution supplied in sterile ampules for IV, intramuscular, or subcutaneous administration containing (per mL) DHE mesylate, USP 1 mg, ethanol, 94% w/w. 6.2% by volume, glycerin 15% by weight, and water for injection.

Other interventions: Matching Placebo for PUR3100
Each capsule of matching placebo is filled with iSPERSE powder comprised of mannitol, leucine, and sodium chloride. The PUR3100 inhalation powder is administered using the supplied RS01 inhalation device (RS01 UHR2, Plastiape S.p.A.).

Other interventions: Matching Placebo for D.H.E 45
The matching placebo for D.H.E. 45 is 0.9% sterile saline for injection.
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety and Tolerability
Timepoint [1] 0 0
Day 1 through Day 3adult subjects
Primary outcome [2] 0 0
Maximum Plasma Concentration [Cmax]
Timepoint [2] 0 0
Day 1 through Day 3
Primary outcome [3] 0 0
Last Observed Plasma Concentration [Clast]
Timepoint [3] 0 0
Day 1 through Day 3
Primary outcome [4] 0 0
Time to Peak Drug Concentration [Tmax]
Timepoint [4] 0 0
Day 1 through Day 3
Primary outcome [5] 0 0
Time of last measurable concentration [Tlast]
Timepoint [5] 0 0
Day 1 through Day 3
Primary outcome [6] 0 0
Area under the curve [AUC (0-t), AUC (0-inf), AUC (0-2h)]
Timepoint [6] 0 0
Day 1 through Day 3
Primary outcome [7] 0 0
Half Life [ t 1/2 ]
Timepoint [7] 0 0
Day 1 through 3
Primary outcome [8] 0 0
Clearance (CL/F)
Timepoint [8] 0 0
Day 1 through Day 3
Primary outcome [9] 0 0
Apparent Volume of Distribution During Terminal Phase (Vz/F)
Timepoint [9] 0 0
Day 1 through Day 3

Eligibility
Key inclusion criteria
1. Male or female subjects aged 18 to 55 years of age with a body mass index =17 and =35
kg/m2.

2. Subject has normal screening and baseline blood pressure, defined as a systolic value
=90 mmHg and =140 mmHg and a diastolic value >60 mmHg and <90 mmHg.

3. Female subjects who are of childbearing potential and male subjects with female
partner(s) of childbearing potential must agree to use an effective contraceptive
throughout the study (e.g., oral contraceptives or Norplant®; a reliable double
barrier method of birth control [diaphragms with contraceptive jelly; cervical caps
with contraceptive jelly; condoms with contraceptive foam]; intrauterine devices;
partner with vasectomy; or abstinence) and for at least 90 days after study drug
administration. In addition, female subjects must have a negative serum pregnancy test
at screening and a negative urine pregnancy test prior to dosing. Note: Women of
non-childbearing potential may be enrolled if they are:

1. Surgically sterile (e.g., hysterectomy with or without oophorectomy; fallopian
tube ligation; endometrial ablation), for at least 30 days prior to signing the
ICF

2. Post-menopausal (= 12 consecutive months of spontaneous amenorrhea and > 50 years
of age)

4. Female subjects must agree not to donate ova/oocytes during the study and for 90 days
after the last dose of IMP.

5. Male subject must agree not to donate semen during the study and for 90 days after the
last dose of IMP.

6. Subject is able and willing to abstain from alcohol for 48 hours prior to admission to
the study unit and throughout the entire study until completion of the Day 7 follow up
visit.

7. Subject is willing to participate in the study, comply with the study requirements,
and voluntarily provide written informed consent.

8. Subject can read, write, and speak English.

9. Subject is mentally competent to provide informed consent.

10. Subject can perform technically acceptable spirometry at screening.

11. Subject can demonstrate the correct inhalation technique for use of the delivery
device and to generate sufficient peak inspiratory flow (PIF) of at least 40 L/min
using the In-Check DIAL device at screening.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Subject has a history of proven or suspected coronary artery disease (CAD), coronary
vasospasm (including Prinzmetal's angina), peripheral vascular disease, or other
ischemic diseases (e.g., ischemic bowel syndrome or Raynaud's syndrome) or cardiac
disorder (e.g., any clinically significant dysrhythmia), any history of heart attack
or stroke, hypertension, diabetes mellitus, liver or kidney disease, aortic aneurysm,
chronic pulmonary disease, or recent (within 3 months) sepsis or vascular surgery.

2. Subject has a current diagnosis of asthma, chronic obstructive pulmonary disease,
active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis,
interstitial lung disease, known alpha-1 antitrypsin deficiency, or other active
pulmonary disease.

3. Subject has clinically significant abnormal laboratory values at screening that, in
the opinion of the investigator would make the subject inappropriate for the study or
put the subject at undue risk, specifically liver function tests (LFTs) >1.5 times the
upper limit of normal (ULN); hemoglobin <10 gm/dL; absolute neutrophil count (ANC)
<2.0 x 109/L; white blood cells (WBC) ?11 x 109/L; platelets <100,000 or >500,000;
international normalization ratio (INR) >1.3.

4. Subject has a QTcF of >450 msec in males or >470 msec in females at screening.

5. Subject has forced expiratory volume in 1 second (FEV1) or forced vital capacity (FVC)
on screening spirometry that is less than 80% predicted.

6. Subject has a history of illicit drug or alcohol abuse within the past 12 months prior
to screening.

7. Subject smokes more than 5 cigarettes per day or vapes more than 5 times per day with
devices that deliver nicotine.

8. Subject has a history of nicotine replacement products daily within 6 months prior to
screening.

9. Subject has a positive alcohol test result at screening.

10. Subject has a positive urine drug test result at screening, unless the result can be
explained by the subject's current medications, in which case the PI should discuss
the disposition of the subject with the Sponsor. Cannabidiol (CDB) and tetrahydro
cannabinol (THC) use is prohibited.

11. Subject has a known sensitivity to the study drug or any of the excipients of the
formulation, or history of clinically significant sensitivity to any agent that, in
the opinion of the investigator, would make participation in the study inadvisable.

12. Subject has donated blood or blood products or had substantial loss of blood (more
than 500 mL) within 6 weeks prior to screening.

13. Subject has participated in an interventional study involving an experimental
therapeutic agent within 3 months of screening.

14. Women who have a positive serum ß-human chorionic gonadotropin (hCG) pregnancy test at
screening or a positive urinary hCG pregnancy test prior to dosing, is pregnant,
lactating, or planning to become pregnant during the study or within 90 days after
conclusion of study participation.

15. Subject has a positive hepatitis B surface antigen (HbsAg), hepatitis C virus (HCV)
antibody or human immunodeficiency virus (HIV) test result. Subjects who are hepatitis
B surface (HBs) antibody positive or hepatitis B (HB) core antibody positive are not
excluded provided the HBsAg result is negative. Subjects who are HCV antibody positive
are not excluded if a subsequent HCV RNA test is negative.

16. Subject has a planned surgery or procedure during participation in the study and for
28 days after the conclusion of study participation.

17. Subject is an employee of the investigator or study site with direct involvement in
the proposed study or other studies under the direction of that investigator or study
site or is a family member of a study site employee or the investigator.

18. Subject has a current or chronic history of liver disease or known hepatic or biliary
abnormalities (except for Gilbert's syndrome or asymptomatic gallstones).

19. The subject is unable or unwilling to comply fully with the study protocol.

20. Subject is mentally or legally incapacitated.

21. Subject is unable or unwilling to undergo multiple venepuncture procedures or the
subject has poor access to veins suitable for cannulation.

22. There is a condition or situation that, in the opinion of the investigator, would make
participation in the study inadvisable.

23. Subject has a history of chronic uncontrolled disease including, but not limited to,
cardiovascular, endocrine, neurological, hepatic, gastrointestinal, renal,
hematologic, urologic, immunologic, or ophthalmic diseases that, in the opinion of the
investigator, would make participation in the study inadvisable.

24. Subject has had major surgery within 6 weeks prior to screening.

25. Subject has a disclosed history, or one known to the investigator, of significant
noncompliance in previous investigational studies or with prescribed medications.

26. Subject requires supplemental oxygen, even on an occasional basis.

27. Subject received a live vaccine within 14 days prior to screening.

28. Caffeine-containing beverage e.g coffee, tea, or caffeine sodas or power drinks
(greater than 3 cups per day, 1 cup=250 mL) within 3 months prior to screening.
Subject is UN able and unwilling to abstain from tea, coffee, or caffeine-containing
beverages for 48 hours prior to admission to the study unit and throughout the entire
study until completion of the Day 7 follow up visit.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Factorial
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
9/06/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
22/09/2022
Sample size
Target
Accrual to date
Final
26
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Nucleus Network Melbourne - Melbourne
Recruitment postcode(s) [1] 0 0
3004 - Melbourne

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Pulmatrix Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
A Double Dummy, Double-blind Study to Assess the Safety, Tolerability, and Pharmacokinetics
of PUR3100 in Healthy Adults
Trial website
https://clinicaltrials.gov/ct2/show/NCT05351086
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries