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CompletedNCT03256552Updated Jan 23, 2018Results posted

Study to Assess the Efficacy and Safety of Three Doses of PT001 in Japanese Subjects With Moderate to Severe COPD

A Phase 2 interventional study of Glycopyrronium MDI 28.8 micrograms and Glycopyrronium MDI 14.4 micrograms in Chronic Obstructive Pulmonary Disease, sponsored by Pearl Therapeutics, Inc.. Completed at 18 sites in Japan. Open to participants aged 40 Years to 80 Years. Per ClinicalTrials.gov, last updated 2018-01-23.

Sponsored by Pearl Therapeutics, Inc. · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
66
Allocation
Randomized
Ages
40 Years to 80 Years
Sex
All
01

Study summary

The overall objective of this study was to assess the efficacy and safety of GP MDI relative to placebo in Japanese subjects with moderate to severe COPD. Each subject received the 4 separate study treatments, scheduled as four, 7-day, treatment periods for a total treatment duration of 28 days.

Read the detailed description

This was a randomized, double-blind, chronic-dosing (7-day), four-period, four-treatment, placebo-controlled, crossover, multi-center study to assess the efficacy and safety of 3 doses of GP MDI (28.8, 14.4, and 7.2 μg ex-actuator, BID) in Japanese subjects with moderate to severe COPD.

Subjects who met the entry criteria had their maintenance therapy for COPD adjusted, as specified in the protocol. To allow for an adequate washout of previous maintenance medications, subjects underwent a washout period of at least 7 days, but not greater than 28 days duration prior to returning to the clinic for Visit 2 (Randomization Visit; Day 1 of Treatment Period 1).

The 4 study treatments were GP MDI 28.8, 14.4, and 7.2 μg ex-actuator, and Placebo MDI BID. Subjects were randomly assigned to 1 of the following 4 treatment sequences (ABCD, BDAC, CADB, DCBA) in a 1:1:1:1 ratio using an Interactive Web Response System where each letter represented 1 of the 4 treatments included in the study by random assignment.

Subjects were to complete 7 days of dosing in each of the 4 Treatment Periods, with each Treatment Period separated by a washout period of 5 to 21 days.

02

Conditions studied

  • Chronic Obstructive Pulmonary Disease
03

Who can participate

Ages eligible
40 Years to 80 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Clinical history of COPD with a moderate to severe classification
  • Current and former smokers with a history of at least 10 pack-years of cigarette smoking.

-Post-bronchodilator FEV1 must be ≥30% and \<80% predicted normal value-

Exclusion criteria

Exclusion Criteria:

  • Pregnancy
  • Primary asthma diagnosis; Poorly controlled COPD defined as acute worsening of COPD that required treatment with corticosteroids or antibiotics in the 6-week interval prior to Screening or between Screening and Visit 2;
  • Clinically significant abnormal ECG
  • Other active pulmonary disease such as active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, primary pulmonary hypertension, interstitial lung disease, and uncontrolled sleep apnea; Cancer that was not in complete remission for at least 5 years;
  • Diagnosis of angle closure glaucoma
  • A documented myocardial infarction within 1 year of Screening.
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
66 participants (actual)

Study arms

  • Active comparator
    GP MDI 28.8 micrograms

    Glycopyrronium Metered Dose Inhaler 28.8 micrograms

    Drug: Glycopyrronium MDI 28.8 micrograms

  • Active comparator
    GP MDI 14.4 micrograms

    Glycopyrronium Metered Dose Inhaler 14.4 micrograms

    Drug: Glycopyrronium MDI 14.4 micrograms

  • Active comparator
    GP MDI 7.2 micrograms

    Glycopyrronium Metered Dose Inhaler 7.2 micrograms

    Drug: Glycopyrronium MDI 7.2 micrograms

  • Placebo comparator
    Placebo MDI

    Placebo Inhalation Aerosol

    Drug: Placebo MDI

Interventions

  • DrugGlycopyrronium MDI 28.8 micrograms

    Glycopyrronium MDI 28.8 micrograms

  • DrugGlycopyrronium MDI 14.4 micrograms

    Glycopyrronium MDI 14.4 micrograms

  • DrugGlycopyrronium MDI 7.2 micrograms

    Glycopyrronium MDI 7.2 micrograms

  • DrugPlacebo MDI

    Placebo Inhalation Aerosol

05

What researchers measure

Primary outcomes

  1. Morning Pre-dose Trough FEV1

    Change from Baseline in Morning Pre-dose Trough FEV1

    Time frame: Baseline, Day 8

Secondary outcomes

  1. FEV1 AUC0-2

    Change from Baseline in FEV1 AUC0-2 normalized for length of follow-up. FEV1 was measured at 15 min, 30 min, 1 hour, and 2 hours post dose.

    Time frame: Day 1 and Day 8

  2. Peak Change in FEV1

    Peak Change from Baseline in FEV1

    Time frame: Day 1 and Day 8

  3. FVC AUC0-2

    Change from Baseline in FVC AUC0-2 on Day 8 normalized for length of follow-up. FVC was measured at 15 min, 30 min, 1 hour, and 2 hours post dose.

    Time frame: Baseline, Day 8

06

Results

Posted Jan 23, 2018

Participant flow

Conducted at 20 sites in Japan from January-September 2015. Entire period of study participation per subject was a maximum of 19 weeks. Planned target enrollment of 60 subjects.

Participant flow — Overall Study
MilestoneOverall Study
Started66
Gp mdi 28.8 µg61
Gp mdi 14.4 µg63
Gp mdi 7.2 µg62
Placebo mdi65
Completed61
Not completed5
Withdrew: Protocol violation1
Withdrew: Physician decision1
Withdrew: Adverse event1
Withdrew: Withdrawal by subject2

Outcome measures

PrimaryMorning Pre-dose Trough FEV1

Change from Baseline in Morning Pre-dose Trough FEV1

Time frame:
Baseline, Day 8
Reported as:
Least squares mean · Liters
Morning Pre-dose Trough FEV1
LitersGP MDI 28.8 µgGP MDI 14.4 µgGP MDI 7.2 µgPlacebo MDI
Morning Pre-dose Trough FEV10.101 (0.068 to 0.134)0.098 (0.066 to 0.131)0.077 (0.045 to 0.110)-0.031 (-0.064 to 0.002)
SecondaryFEV1 AUC0-2

Change from Baseline in FEV1 AUC0-2 normalized for length of follow-up. FEV1 was measured at 15 min, 30 min, 1 hour, and 2 hours post dose.

Time frame:
Day 1 and Day 8
Reported as:
Least squares mean · Liters
FEV1 AUC0-2
LitersGP MDI 28.8 µgGP MDI 14.4 µgGP MDI 7.2 µgPlacebo MDI
Day 10.176 (0.146 to 0.205)0.140 (0.111 to 0.170)0.127 (0.098 to 0.157)0.043 (0.014 to 0.073)
Day 80.194 (0.157 to 0.230)0.199 (0.162 to 0.236)0.170 (0.133 to 0.206)0.019 (-0.018 to 0.055)
SecondaryPeak Change in FEV1

Peak Change from Baseline in FEV1

Time frame:
Day 1 and Day 8
Reported as:
Least squares mean · Liters
Peak Change in FEV1
LitersGP MDI 28.8 µgGP MDI 14.4 µgGP MDI 7.2 µgPlacebo MDI
Day 10.254 (0.219 to 0.289)0.212 (0.177 to 0.247)0.192 (0.157 to 0.227)0.104 (0.069 to 0.139)
Day 80.260 (0.219 to 0.301)0.265 (0.224 to 0.306)0.238 (0.197 to 0.279)0.082 (0.041 to 0.124)
SecondaryFVC AUC0-2

Change from Baseline in FVC AUC0-2 on Day 8 normalized for length of follow-up. FVC was measured at 15 min, 30 min, 1 hour, and 2 hours post dose.

Time frame:
Baseline, Day 8
Reported as:
Least squares mean · Liters
FVC AUC0-2
LitersGP MDI 28.8 µgGP MDI 14.4 µgGP MDI 7.2 µgPlacebo MDI
FVC AUC0-20.273 (0.207 to 0.339)0.265 (0.199 to 0.331)0.223 (0.157 to 0.288)0.047 (-0.019 to 0.113)

Adverse events

Collected over Adverse events were collected from the time the subject signed consent up to the follow-up visit 7-14 days after last dose of study drug.. Non-serious events are listed at a 3% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
GP MDI 28.8 µg—0/61 (0%)2/61 (3.3%)
GP MDI 14.4 µg—0/63 (0%)2/63 (3.2%)
GP MDI 7.2 µg—0/62 (0%)1/62 (1.6%)
Placebo MDI—1/65 (1.5%)1/65 (1.5%)
Most frequent serious events
Most frequent serious events
EventGP MDI 28.8 µgGP MDI 14.4 µgGP MDI 7.2 µgPlacebo MDI
PneumoniaInfections and infestations0/610/630/621/65
Chronic Obstructive Pulmonary DiseaseRespiratory, thoracic and mediastinal disorders0/610/630/621/65
Most frequent other events
Most frequent other events
EventGP MDI 28.8 µgGP MDI 14.4 µgGP MDI 7.2 µgPlacebo MDI
RashSkin and subcutaneous tissue disorders2/610/630/620/65
NasopharyngitisInfections and infestations0/612/631/621/65

Baseline characteristics

MITT Population defined as all subjects who received treatment and had post-treatment efficacy data from at least two treatment periods.

Age, Continuous
Age, Continuous(Years)All Subjects
Mean67.5 ± 7.0
Sex: Female, Male
Sex: Female, Male(Participants)All Subjects
Female3
Male59
07

Study locations

18 sites
  • Pearl Investigative Site
    Fukuoka-shi, Fukuoka-Ken, Japan
  • Pearl Investigative Site
    Iizuka-shi, Fukuoka-Ken, Japan
  • Pearl Investigative Site
    Mizunami-shi, Gifu-Ken, Japan
  • Pearl Investigative Site
    Sapporo-shi, Hokkaido, Japan
  • Pearl Investigative Site
    Ako-shi, Hyogo-Ken, Japan
  • Pearl Investigative Site
    Kakogawa-shi, Hyogo-Ken, Japan
  • Pearl Investigative Site
    Kobe-Shi, Hyogo-Ken, Japan
  • Pearl Investigative Site
    Nishinomiya-shi, Hyogo-Ken, Japan
  • Pearl Investigative Site
    Himeji-shi, Hyogo, Japan
  • Pearl Investigative Site
    Naka-gun, Ibaraki-Ken, Japan
  • Pearl Investigative Site
    Kawasaki-shi, Kanagawa-Ken, Japan
  • Pearl Investigative Site
    Kyoto-shi, Kyoto-Fu, Japan
  • Pearl Investigative Site
    Kasaoka-shi, Okayama-Ken, Japan
  • Pearl Investigative Site
    Kishiwada-shi, Osaka-Fu, Japan
  • Pearl Investigative Site
    Osaka-shi, Osaka-Fu, Japan
  • Pearl Investigative Site
    Hamamatsu-shi, Shizuoka-Ken, Japan
  • Pearl Investigative Site
    Chuo-ku, Tokyo-To, Japan
  • Pearl Investigative Site
    Toshima-ku, Tokyo-To, Japan
08

References and documents

Publications

  • Fukushima Y, Nakatani Y, Ide Y, Sekino H, St Rose E, Siddiqui S, Maes A, Reisner C. Randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of three doses of co-suspension delivery technology glycopyrronium MDI in Japanese patients with moderate-to-severe COPD. Int J Chron Obstruct Pulmon Dis. 2018 Apr 13;13:1187-1194. doi: 10.2147/COPD.S159246. eCollection 2018. PubMed 29695902 ↗
09

Registry details

Key details

Study ID
NCT03256552
Lead sponsor
Pearl Therapeutics, Inc.
Responsible party
Sponsor
First posted
Aug 22, 2017
Start date
Jan 28, 2015
Primary completion
Sep 5, 2015
Completion
Sep 5, 2015
Results posted
Jan 23, 2018
Last update
Jan 23, 2018

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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