CClinicalTrials.gg
Sign In
CompletedNCT01189396Updated Jul 2, 2017

Escalating and Cumulative-Dose Study of Pharmacokinetics (PK), Pharmacodynamics (PD) and Safety of A006

A Phase 2 interventional study of A006 and Placebo DPI in Asthma, Bronchospasm and Chronic Obstructive Pulmonary Disease (COPD), sponsored by Amphastar Pharmaceuticals, Inc.. Completed at 4 sites in United States. Open to participants aged 18 Years to 55 Years. Per ClinicalTrials.gov, last updated 2017-07-02.

Sponsored by Amphastar Pharmaceuticals, Inc. · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
27
Allocation
Randomized
Ages
18 Years to 55 Years
Sex
All
01

Study summary

The main objective is to evaluate the bronchodilatory efficacy, safety and pharmacokinetic profiles of A006 (Albuterol Dry Powder Inhaler (DPI)), in comparison with those of an active control, Proventil-HFA (Albuterol Metered Dose Inhaler (MDI)), and a Placebo DPI in escalating and cumulative-doses up to 1440 mcg, eight (8) times of the proposed clinical dose.

02

Conditions studied

  • Asthma
  • Bronchospasm
  • Chronic Obstructive Pulmonary Disease (COPD)

Keywords

  • asthma
  • bronchospasm
  • COPD
  • reversibility
  • efficacy
03

Who can participate

Ages eligible
18 Years to 55 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Body weight ≥ 50 kg for men and ≥ 45 kg for women, and BMI within the range of 18.5 - 30.0 kg/m2 inclusive;
  • Sitting blood pressure ≤ 135/90 mmHg;
  • Demonstrating negative alcohol/drug screen tests;
  • Demonstrating negative HIV, HBsAg and HCV-Ab screen tests;
  • With mild-to-moderate persistent asthma for at least 6 months prior to Screening, and having used inhaled β-agonist(s) for asthma control;
  • Demonstrating a Mean Screening Baseline FEV1 at 50.0 - 85.0 % of predicted normal;
  • Demonstrating a ≥ 15.0% Airway Reversibility in FEV1 within 30(±5) min after inhaling 2 actuations of Proventil-HFA;
  • Demonstrating Peak Inspiratory Flow Rate within 80-150 L/min;
  • Demonstrating proficiency in the use of DPI and MDI after training;
  • Females of child-bearing potential must be non-pregnant, non-lactating, and practicing a clinically acceptable form of birth control;
  • Having properly consented to participate in the trial.

Exclusion criteria

Exclusion Criteria:

  • Smoking history of ≥ 10 pack-years, or having smoked within 6 months prior to Screening;
  • Upper respiratory tract infections within 2 wk, or lower respiratory tract infection within 4 wk;
  • Asthma exacerbations that required emergency care or hospitalized treatment, within 4 wk prior;
  • Any current or recent respiratory conditions that might significantly affect pharmacodynamic response to the study drugs, besides asthma;
  • Concurrent clinically significant cardiovascular, hematological, renal, neurologic, hepatic, endocrine, psychiatric, malignancies, or other illnesses that could impact on the conduct, safety and evaluation of the study;
  • Known intolerance or hypersensitivity to any of the ingredients of the A006 or Proventil-HFA;
  • Use of prohibited drugs or failure to observe the drug washout restrictions;
  • Having been on other clinical drug/device studies in the last 30 days;
  • Having donated blood within the last 30 days prior to Screening.
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
Triple (Participant, Investigator, Outcomes assessor)
Enrollment
27 participants (actual)

Study arms

  • Experimental
    T

    Four doses of A006 taken in 30 minute intervals. Doses will have an escalating number of inhalations (1, 1, 2, and 4 inhalations). Total cumulative Albuterol dose at 90 minutes is 1440 mcg.

    Drug: A006

  • Active comparator
    R

    Four doses of Proventil-HFA taken in 30 minute intervals. Doses will have an escalating number of inhalations (2, 2, 4, and 8 inhalations). Total cumulative Albuterol dose at 90 minutes is 1440 mcg.

    Drug: Proventil-HFA

  • Placebo comparator
    P

    Four doses of Placebo DPI taken in 30 minute intervals. Doses will have an escalating number of inhalations (1, 1, 2, and 4 inhalations). Total cumulative Albuterol dose at 90 minutes is 0 mcg.

    Drug: Placebo DPI

Interventions

  • DrugA006

    Albuterol DPI with 180 mcg Albuterol/inhalation

  • DrugPlacebo DPI

    Placebo DPI with 0 mcg Albuterol/inhalation

  • DrugProventil-HFA

    Albuterol MDI with 90 mcg Albuterol/inhalation

05

What researchers measure

Primary outcomes

  1. Bronchodilatory efficacy after the escalating and cumulative-doses, up to 1,440 mcg.

    Area Under the Curve (AUC)0-t of percent change in Forced Expiratory Volume in 1 second (FEV1), which is defined as the area under curve of post-dose FEV1 percentage changes from the Pre-dose Baseline FEV1 (FEV10) versus time. Doses are at 0, 30, 60 and 90 min.

    Time frame: -15 min predose, 15 min post dose 1, 2 and 3 and 15, 45, 90, 120, 180, 240, 360 min post dose 4

Secondary outcomes

  1. AUC0-t of change in FEV1

    AUC of FEV1 volume post-dose changes (change in Volume) from the Pre-dose Baseline FEV1 (FEV10). Doses are at 0, 30, 60 and 90 min.

    Time frame: -15, 15 min post 1, 2, and 3, and 15, 90, 120, 240, and 360min post dose 4

  2. Time to onset

    Time to onset of bronchodilatory effect, determined by linear interpolation as the point where FEV1 % change first reaches ≥ 12% from FEV10.

    Time frame: 0 - 120 min

  3. Peak Response

    The peak bronchodilator response, defined as the maximum post-dose FEV1 % change. Doses are at time 0, 30, 60, and 90 min.

    Time frame: 15 min post dose 1, 2 and 3 and 15, 45, 90, 120, 180, 240, and 360 min post dose 4

  4. Adverse Events

    The adverse drug events (ADE) that are observed with Proventil-HFA may be expected with the use of A006

    Time frame: Time 0, 15, 45, 75, 105, 150, 195, 130, 190, 250, 435 minutes post dose 1

  5. Blood Analysis

    serum glucose and potassium analysis and PK analysis

    Time frame: -15, 10, 25,40, 55, 70, 85, 95, 115, 145, 175, 210, 270, 330, 690 min post dose 1

  6. Vital Signs and Electrocardiogram (ECG)

    vital signs, including pulse and blood pressure and 12-lead ECG

    Time frame: -15, 5, 35, 65, 100, 155, 275, 455, 815 min post dose 1

06

Study locations

4 sites
  • Amphastar Site 0025
    Medford, Oregon 97504, United States
  • Amphastar Site 0026
    Portland, Oregon 97213, United States
  • Amphastar Site 0032
    San Antonio, Texas 78229, United States
  • Amphastar Site 0034
    Seattle, Washington 98105, United States
07

References and documents

Publications

  • Ahrens RC. The role of the MDI and DPI in pediatric patients: "Children are not just miniature adults". Respir Care. 2005 Oct;50(10):1323-8; discussion 1328-30. PubMed 16185368 ↗
  • Goldstein DA, Tan YK, Soldin SJ. Pharmacokinetics and absolute bioavailability of salbutamol in healthy adult volunteers. Eur J Clin Pharmacol. 1987;32(6):631-4. doi: 10.1007/BF02456001. PubMed 3653233 ↗
  • Hindle M, Newton DA, Chrystyn H. Dry powder inhalers are bioequivalent to metered-dose inhalers. A study using a new urinary albuterol (salbutamol) assay technique. Chest. 1995 Mar;107(3):629-33. doi: 10.1378/chest.107.3.629. PubMed 7874928 ↗
  • Miller MR, Crapo R, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Enright P, van der Grinten CP, Gustafsson P, Jensen R, Johnson DC, MacIntyre N, McKay R, Navajas D, Pedersen OF, Pellegrino R, Viegi G, Wanger J; ATS/ERS Task Force. General considerations for lung function testing. Eur Respir J. 2005 Jul;26(1):153-61. doi: 10.1183/09031936.05.00034505. No abstract available. PubMed 15994402 ↗
  • Pellegrino R, Viegi G, Brusasco V, Crapo RO, Burgos F, Casaburi R, Coates A, van der Grinten CP, Gustafsson P, Hankinson J, Jensen R, Johnson DC, MacIntyre N, McKay R, Miller MR, Navajas D, Pedersen OF, Wanger J. Interpretative strategies for lung function tests. Eur Respir J. 2005 Nov;26(5):948-68. doi: 10.1183/09031936.05.00035205. No abstract available. PubMed 16264058 ↗
  • Crapo RO, Morris AH, Gardner RM. Reference spirometric values using techniques and equipment that meet ATS recommendations. Am Rev Respir Dis. 1981 Jun;123(6):659-64. doi: 10.1164/arrd.1981.123.6.659. PubMed 7271065 ↗
  • Crapo RO, Morris AH, Clayton PD, Nixon CR. Lung volumes in healthy nonsmoking adults. Bull Eur Physiopathol Respir. 1982 May-Jun;18(3):419-25. PubMed 7074238 ↗
08

Registry details

Key details

Study ID
NCT01189396
Lead sponsor
Amphastar Pharmaceuticals, Inc.
Responsible party
Sponsor
First posted
Aug 26, 2010
Start date
Jul 2010
Primary completion
Dec 2010
Completion
Jan 2011
Last update
Jul 2, 2017

Study contacts

Safety Monitor
study director · Amphastar Pharmaceuticals, Inc.

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Jun 2017. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Asthma→

Other studies from this sponsor

Amphastar Pharmaceuticals, Inc.

Start the discussion