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Trial registered on ANZCTR


Registration number
ACTRN12615000654550
Ethics application status
Approved
Date submitted
7/06/2015
Date registered
25/06/2015
Date last updated
14/12/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Assessment of Citramel in Patients with Cystic Fibrosis
Scientific title
A Double-blind Randomised Placebo-controlled Cross-Over Study of the Effects of Citramel on the Signs and Symptoms of Cystic Fibrosis
Secondary ID [1] 286869 0
BE10-1001
Universal Trial Number (UTN)
U1111-1171-1611
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cystic Fibrosis 295270 0
Condition category
Condition code
Respiratory 295520 295520 0 0
Other respiratory disorders / diseases
Human Genetics and Inherited Disorders 295521 295521 0 0
Cystic fibrosis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Citramel - an aqueous solution of sodium citrate (16.18 mg/mL), citric acid (0.046 mg/mL) and ammonium chloride (4.12 mg/mL). Administered by aerosol twice daily (morning and night) for 28 days. This study is a randomised crossover design and there is a washout period of 14 days before the second study treatment is started.

For patients being treated with Tobramycin: this should be administered at least ten minutes after completion of the inhalation of study medication is inhaled. Note that the nebulizing equipment provided for the study medications should NOT be used to administer tobramycin.
Intervention code [1] 292047 0
Treatment: Drugs
Comparator / control treatment
Placebo: normal saline. Administered by aerosol twice daily (morning and night) for 28 days. Patients will have a 14 day washout period between receiving Citramel and 28 days treatment with placebo in a randomised cross-over design. For patients being treated with Tobramycin: this should be administered at least ten minutes after completion of the inhalation of study medication is inhaled. Note that the nebulizing equipment provided for the study medications should NOT be used to administer tobramycin.
Compliance will be assessed by checking the vials returned by study participants.
Control group
Placebo

Outcomes
Primary outcome [1] 295253 0
Safety as measured by adverse events, Laboratory tests, vital signs and patient diary
Timepoint [1] 295253 0
Screening/baseline, Day 3 or 4, weeks 1, 2, 3 and 4 of each of the two treatment periods. Adverse events also assessed at two weeks post last dose of Week 4 of each of the two treatment periods.
Secondary outcome [1] 315193 0
Absolute change in FEV1 between Citramel inhalation and placebo inhalation
Timepoint [1] 315193 0
at the end of each treatment period (Day 28) compared with Baseline for that treatment phase.
Secondary outcome [2] 315194 0
Change in Spirometry measures (FVC and FEV1 % of predicted) between Citramel inhalation and placebo inhalation
Timepoint [2] 315194 0
at the end of each treatment period (Day 28) compared with Baseline for that treatment phase
Secondary outcome [3] 315195 0
Incremental AUC of the spirometry measures (FVC and FEV1 % of predicted) between Citramel inhalation and placebo inhalation.
Timepoint [3] 315195 0
From baseline to day 28 for each treatment phase
Secondary outcome [4] 315196 0
Rheology assessments of sputum samples between Citramel inhalation and placebo inhalation Rheology assessments include in vitro ciliary transportability (MCTR), mucus hydration (% solids), and in vitro cough transportability (CTR). Sputum production from CF patients may be very variable. The rheological analysis may only be conducted if a suitable set and number of sputum samples are obtained.
Timepoint [4] 315196 0
From baseline to end of each treatment phase (day 28)
Secondary outcome [5] 315197 0
Comparison of the sputum volume between Citramel inhalation and placebo inhalation. Sputum volume will determined using a measuring cylinder.
Timepoint [5] 315197 0
At the end of each treatment period (Day 28) compared with Baseline for that treatment phase
Secondary outcome [6] 315198 0
Comparison of the number and type of organisms cultured (using standard microbiology laboratory procedures) from sputum samples between Citramel inhalation and placebo inhalation
Timepoint [6] 315198 0
At the end of each treatment period (day 28) compared with Baseline for that treatment phase
Secondary outcome [7] 315199 0
Comparison of the Participant self-assessment of efficacy between Citramel inhalation and placebo inhalation (10cm visual analogue (VAS) scale)
Timepoint [7] 315199 0
At the end of each treatment period (Day 28) compared with Baseline for that treatment phase
Secondary outcome [8] 315200 0
Comparison of CFQ-R questionnaire between Citramel and placebo
Timepoint [8] 315200 0
At the end of each treatment period (Day 28) compared with Baseline for that treatment phase
Secondary outcome [9] 315201 0
Comparison of CFTSSD questionnaire between Citramel and placebo
Timepoint [9] 315201 0
At the end of each treatment period (Day 28) compared with Baseline for that treatment phase
Secondary outcome [10] 315202 0
Comparison of Participant self-assessment of satisfaction with the treatment and tolerability of the treatment. Five-point likert rating scales will be used with options from 'very unsatisfied / very poor' to 'very satisfied / very good'
Timepoint [10] 315202 0
At the end of each treatment period (Day 28) compared with Baseline for that treatment phase

Eligibility
Key inclusion criteria
Confirmed diagnosis of cystic fibrosis; aged at least 16 years who provide written informed consent; sexually active females must use contraception; stable medications; FEV1 between 40-100% of normal range.
Minimum age
16 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Clinically significant co-existing disease; current or previous clinically significant smoking history; ECG or blood pressure abnormalities; use of a bronchodilator within 12hrs prior to bronchodilator challenge at screening; renal impairment; elevated liver enzymes;

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)
After obtaining consent and confirming eligibility, the participant will be enrolled in the study. Each participant will receive both Citramel and placebo in a cross-over study
design. All study staff will remain blinded; Citramel and matching placebo inhalations will be provided by the Sponsor. Individual randomisation envelopes will be provided in case the identity of study drug administered to a participant for a treatment phase needs to be known.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomization by computer
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
Intervention assignment
Crossover
Other design features
Phase
Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
A sample size of 20 completed participants will provide >80% power to detect an effect size for the differential change in the absolute FEV1 with Citramel compared with placebo of 0.70 or more as statistically significant (two-tailed a=0.05). Assuming the standard deviation of the differential change is 0.5L the study is adequately powered to detect a difference of approximately 0.35L. Therefore approx. 24 patients will be randomised to allow for 4 patients to drop-out before completing the study.


The primary analysis of study efficacy measures will be performed using the EP population. Additional analyses of all efficacy measures using the ITT will also be performed if the EPP is < 80 % of the ITT population.
Standard descriptive statistics (including means, standard deviations, standard errors, medians, ranges and frequencies), graphs, and participant data listings will be used to summarize the baseline demographic and clinical characteristics, and the efficacy and safety data at relevant time-points. Tabular and graphical summaries will represent
participant groups. Participant data listings will present data by treatment group.

Primary Safety Analyses
Adverse events over the period of the study will be individually listed by treatment groups. The incidences and percentages of individuals experiencing AEs within each treatment group will be summarized by System Organ Class (SOC) with further summaries by severity and relatedness (causality) categories. The more common AEs maybe
compared between treatment groups using Fisher’s exact tests. The safety analyses will be performed using the Safety population.

Primary Efficacy Analyses
The primary analyses will compare the changes in the absolute FEV1 between the two randomised treatments. A general linear model will be used for this comparison with treatment sequence included as a between-subjects term in the model. Individual group changes and the difference in the changes will be summarised with 95 % confidence intervals. A two-sided p-value of 0.05 will be used to indicate statistical
significance.

Secondary Efficacy Analyses
The secondary efficacy analyses will compare the changes in the absolute FEV1 between the two randomised treatments. A general linear model will be used for this comparison with treatment sequence included as a between-subjects term in the model. Individual group changes and the difference in the changes will be summarised with 95 % confidence
intervals. A two-sided p-value of 0.05 will be used to indicate statistical significance.
The questionnaire, self-assessment data collected at weeks 4 and 12 will be compared using a general linear model including a between subjects term for treatment sequence. Individual group means and the difference in the means will be summarised with 95 % confidence intervals. A two-sided p-value of 0.05 will be used to indicate statistical significance.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 6958 0
New Zealand
State/province [1] 6958 0
Canterbury
Country [2] 7878 0
New Zealand
State/province [2] 7878 0
Auckland
Country [3] 8755 0
New Zealand
State/province [3] 8755 0
Otago
Country [4] 8756 0
New Zealand
State/province [4] 8756 0
Waikato

Funding & Sponsors
Funding source category [1] 291427 0
Commercial sector/Industry
Name [1] 291427 0
Breathe easy Ltd
Address [1] 291427 0
Ground Floor, Shed 20,
139 Quay Street,
Princes Wharf
Auckland 1010
Country [1] 291427 0
New Zealand
Funding source category [2] 291428 0
Government body
Name [2] 291428 0
NZVIF (New Zealand Venture Investment Fund)
Address [2] 291428 0
Unit 1B, Ascot Office Park, 93-95 Ascot Ave
Green Lane, Auckland 1051, New Zealand
Country [2] 291428 0
New Zealand
Primary sponsor type
Commercial sector/Industry
Name
Breathe Easy Ltd
Address
Ground Floor, Shed 20,
139 Quay Street,
Princes Wharf
Auckland 1010
Country
New Zealand
Secondary sponsor category [1] 290104 0
None
Name [1] 290104 0
Address [1] 290104 0
Country [1] 290104 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292980 0
Central Health and Disability Ethics Committee
Ethics committee address [1] 292980 0
1 The Terrace
C/- MEDSAFE, Level 6, Deloitte House
10 Brandon Street
PO Box 5013
Wellington
6011
Ethics committee country [1] 292980 0
New Zealand
Date submitted for ethics approval [1] 292980 0
Approval date [1] 292980 0
01/07/2014
Ethics approval number [1] 292980 0
14/CEN/89

Summary
Brief summary
This is a research study to evaluate Citramel inhalation. It is a double-blind, placebo, cross-over design to assess the safety, tolerability and efficacy of Citramel in approx. 24 cystic fibrosis patients.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 57890 0
Dr Chris Wynne
Address 57890 0
Christchurch Clinical Studies Trust (CCST) 31 Tuam Street Christchurch 8011
Country 57890 0
New Zealand
Phone 57890 0
+64 3 372 9477
Fax 57890 0
+64 3 372 9478
Email 57890 0
Chris@ccst.co.nz
Contact person for public queries
Name 57891 0
Mr Jon Broadley
Address 57891 0
Breathe Easy Ltd, Whitecliff College of Arts and Design Building, 24 Balfour Road, Parnell, Auckland 1052, New Zealand
Country 57891 0
New Zealand
Phone 57891 0
+64 272 333 111
Fax 57891 0
Email 57891 0
jon@strategyplus.nz
Contact person for scientific queries
Name 57892 0
Mr Jon Broadley
Address 57892 0
Breathe Easy Ltd, Whitecliff College of Arts and Design Building, 24 Balfour Road, Parnell, Auckland 1052, New Zealand
Country 57892 0
New Zealand
Phone 57892 0
+64 272 333 111
Fax 57892 0
Email 57892 0
jon@strategyplus.nz

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary