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Trial registered on ANZCTR


Registration number
ACTRN12615000199516
Ethics application status
Approved
Date submitted
18/02/2015
Date registered
2/03/2015
Date last updated
27/06/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
A study to evaluate the safety, tolerability, pharmacokinetics and analgesic efficacy of oral CMX-020 in healthy male and female subjects.
Scientific title
A Randomized, Double-Blind, Placebo-Controlled, Analytically Masked Sequential-Panel, Ascending Single-Dose, and Repeated Twice Daily-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Analgesic Efficacy of Oral CMX-020 in Healthy Male and Female Subjects.
Secondary ID [1] 286189 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic pain 294218 0
Condition category
Condition code
Other 294539 294539 0 0
Conditions of unknown or disputed aetiology (such as chronic fatigue syndrome/myalgic encephalomyelitis)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The interventional product, CMX-020, will be administered as an oral capsule.

CMX-020 and matching placebo will be provided as 10 mg capsules. Depending on the dose level, subjects will take 5, 10 or 20 capsules to provide 50 mg, 100 mg and 200 mg per dose.

The starting dose of 50 mg oral CMX-020 for the present study is consistent with the Maximum Recommended Starting Dose (MRSD) proposed in the Food and Drug Administration Guidance, 2005. The 50 mg starting dose is well within the 1/10th of the NOAEL safety margin established in the 14-day repeat dose study in monkey.
Subsequent treatment groups (100 mg and 200 mg) will be dosed in an escalating order, each dose level increased by no more than 2-fold over the previous dose level.

Subjects will be administered a single oral dose of CMX-020/placebo on Day 1 (fasted dose) and then a single oral dose of CMX-020/placebo on Day 8 (fed dose), followed by twice daily dosing of oral CMX-020/placebo from morning of Day 9 (fasted) through to morning of Day 13 (fasted) i.e. from Day 9 to Day 13, the subject will be administered 2 X 50mg doses per day for Cohort 1, 2 X 100mg doses per day for Cohort 2 and 2 X 200mg doses per day for Cohort 3.

Every effort will be made to administer each dose of CMX-020 or matching placebo with 240 mL of room temperature water, particularly with the 0, 168 and 288 hour (PK) doses. If absolutely necessary, an additional amount of up to 240 mL of water may be taken to facilitate capsule ingestion and any additional amount recorded in the CRF.

All medications will be administered in the clinical study unit under the supervision of study staff. Research personnel will ensure each study drug dose has been ingested by performing a hand and mouth check.
Intervention code [1] 291210 0
Treatment: Drugs
Comparator / control treatment
The comparator/ control for this trial is oral 10 mg capsule of matching placebo.
Control group
Placebo

Outcomes
Primary outcome [1] 294319 0
1. To evaluate the safety and tolerability of escalating single and multiple doses of CMX-020 administered orally to healthy male and female subjects;

Parameters assessed for safety include adverse events, serious adverse events, oxygen saturation, physical examination including vitals, clinical laboratory values, ECG and drug feel and drug likeability ratings which is a visual analog scale.
Timepoint [1] 294319 0
Measurements to be taken daily upto Day 14 except Day 6 following single and multiple oral doses of CMX-020/placebo.
Primary outcome [2] 294323 0
2. To determine the maximum tolerated dose (MTD) of CMX-020 administered orally to healthy male and female subjects.

Blood assessments would be done to determine the MTD
Timepoint [2] 294323 0
Single dose (fasted) PK analysis - To be assessed 20 times on Day 1 (pre-dose, and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 10, 12, 14, 16, 20 and 24 hours post-dose) and once daily on Day 3 (48 hour), 4 (72 hour), 5 (96 hour) post Day 1 dose.
Single dose (fed) PK analysis - To be assessed 20 times on Day 8 (pre-dose, and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 10, 12, 14, 16, 20 and 24 hours post Day 8 dosing)
Multiple dose (fasted) PK analysis - To be assessed once daily on Day 10 (48 hour), 11 (72 hour), 12 (96 hour) post Day 8 dosing and 20 times on Day 13 (pre-dose, and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 10, 12, 14, 16, 20 and 24 hours post Day 13 dosing).
36 hours post Day 13 dosing PK sample is optional, based on PI discretion on review of earlier PK data.
Secondary outcome [1] 313030 0
1. To evaluate the pharmacokinetics of escalating single and multiple doses of CMX-020 administered orally to healthy male and female subjects.

Blood assessments would be carried out for PK analysis
Timepoint [1] 313030 0
Single dose (fasted) PK analysis - To be assessed 20 times on Day 1 (pre-dose, and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 10, 12, 14, 16, 20 and 24 hours post-dose) and once daily on Day 3 (48 hour), 4 (72 hour), 5 (96 hour) post Day 1 dose.
Single dose (fed) PK analysis - To be assessed 20 times on Day 8 (pre-dose, and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 10, 12, 14, 16, 20 and 24 hours post Day 8 dosing)
Multiple dose (fasted) PK analysis - To be assessed once daily on Day 10 (48 hour), 11 (72 hour), 12 (96 hour) post Day 8 dosing and 20 times on Day 13 (pre-dose, and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 10, 12, 14, 16, 20 and 24 hours post Day 13 dosing).
36 hours post Day 13 dosing PK sample is optional, based on PI discretion on review of earlier PK data.
Secondary outcome [2] 313031 0
2. To evaluate the bioavailability of CMX-020 administered orally to healthy male and female subjects under fed and fasted conditions;

Blood assessments would be carried out for evaluation of bioavailability.
Timepoint [2] 313031 0
Single dose (fasted) PK analysis - To be assessed 20 times on Day 1 (pre-dose, and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 10, 12, 14, 16, 20 and 24 hours post-dose) and once daily on Day 3 (48 hour), 4 (72 hour), 5 (96 hour) post Day 1 dose.
Single dose (fed) PK analysis - To be assessed 20 times on Day 8 (pre-dose, and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 10, 12, 14, 16, 20 and 24 hours post Day 8 dosing)
Multiple dose (fasted) PK analysis - To be assessed once daily on Day 10 (48 hour), 11 (72 hour), 12 (96 hour) post Day 8 dosing and 20 times on Day 13 (pre-dose, and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 10, 12, 14, 16, 20 and 24 hours post Day 13 dosing).
36 hours post Day 13 dosing PK sample is optional, based on PI discretion on review of earlier PK data.
Secondary outcome [3] 313032 0
3. To explore antinociceptive effects of CMX-020 administered orally to healthy male and female subjects.

Cold pressor test would be used for assessment of nociceptive effects where continuous non-invasive hemodynamic monitoring will be performed using the Nexfin (Registered Trademark) system with mean arterial blood pressure output from the device serving as a surrogate marker to the response on to the Cold Pressor Test.
Timepoint [3] 313032 0
Assessments would be done on Day -1 (baseline), Day 1 (2.5-4.0 hour post dose) and Day 10/ Day 11 (2-3.5 hour post morning dose) wherein the first five subjects with an even randomisation number will be tested on Day 10 while the remaining five would be tested on Day 11.

Eligibility
Key inclusion criteria
- if female of child bearing potential; must be surgically sterile, or practicing a medically acceptable form of contraception. Must have a negative urine pregnancy test at screening and check-in and be non-lactating.
- if male; must agree to use a condom if engaging in sexual intercourse at any time during the study.
- good health as determined by a physician.
- clinical lab results within reference range unless results are deemed not clinically significant by Investigator or Sponsor, or normal upon retesting during the screening and check-in periods.
- BMI between 21 and 30 kg/m2, inclusive.
- negative urine toxicology screen for substances of abuse and a negative alcohol breath screen during screening and check-in.
- negative for hepatitis B surface antigen, hepatitis C antibody and HIV at screening visit.
- creatinine clearance of at least 70 mL/min during screening.
Minimum age
18 Years
Maximum age
50 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- history of injury or disease involving either hand.
- history of drug or alcohol abuse within the past 2 years.
- previous history of cancer, other than basal cell or Stage 1 squamous cell carcinoma of the skin, that has not been in remission for at least 5 years prior to dose of study drug.
- systolic BP >140 mm Hg or < 85 mm Hg, or diastolic BP > 90 or < 60 mm of Hg at screening or check-in.
- pulse > 100 beats/minute or < 55 beats /minute during screening or check-in.
- medical history of hypertension, hypotension or postural hypotension.
- history of any acute or chronic painful condition requiring frequent analgesic use.
- pain at the time of check-in or morning of Day 1 which would warrant analgesia during the study or potentially interfere with pain assessments.
- history or family history of seizure.
- history of head trauma requiring an ER visit, inpatient observation or hospitalization.
- history of syncope.
- history or clinical manifestations of significant metabolic, hematologic, pulmonary, cardiovascular, gastrointestinal, neurologic, hepatic, renal, urologic, immunologic, or psychiatric disorders.
- clinically significant abnormal ECG at screening.
- history of long QT syndrome or a QTcF interval > 450 msec at screening.
- unwilling to abstain from grapefruit, grapefruit juice, or any caffeine-containing products or medications for 72 hours prior to study drug administration and throughout study.
- consumed alcohol within 72 hours prior to screening or baseline/check-in visits.
- used any tobacco products within 6 weeks prior to screening.
- dietary restrictionsand poor venous access.
- used any prescription, OTC, nutraceuticals, herbal or homeopathic medication or vitamins within 14 days prior to study drug administration.
- donated blood within 30 days prior to check-in visit.
- participated in an investigational study within past 30 days or 5 half lives of the investigational drug (whichever is longer) prior to study drug administration.

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 informed consent has been obtained, all screening tests establishing subject eligibility will be performed within a period of 21 days before dosing. Subjects will be admitted to the clinical facility on Day -1.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
In this study there are 3 dose groups (cohorts), each consisting of 10 subjects (5 males and 5 females); 8 will be randomised to receive study drug/ oral CMX-020 (4 males and 4 females) and 2 will receive placebo (1 male and 1 female).
Thus approximately 30 healthy male and female subjects 18-50 years of age will be enrolled into the study.
Additional cohorts may be added based on safety and tolerability in previous cohorts, subject to HREC approval.

Subjects will be administered a single oral dose of CMX-020/placebo on Day 1 (fasted dose) and then a single oral dose of CMX-020/placebo on Day 8 (fed dose), followed by twice daily dosing of oral CMX-020/placebo from morning of Day 9 (fasted) through to morning of Day 13 (fasted).

Allocation will be concealed by use of pre labelled drug boxes containing subject randomisation numbers and use of sealed opaque envelopes.

Computerised generated randomisation schedule using SAS software will be used for treatment allocation (sequence generation).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Other
Other design features
Sequential panel, dose escalating single and multiple dose study.
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
27/02/2015
Actual
28/02/2015
Date of last participant enrolment
Anticipated
3/05/2015
Actual
20/04/2015
Date of last data collection
Anticipated
Actual
Sample size
Target
30
Accrual to date
Final
31
Recruitment in Australia
Recruitment state(s)
SA
Recruitment postcode(s) [1] 9241 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 290763 0
Commercial sector/Industry
Name [1] 290763 0
Cytometix Australia Pty Ltd
Country [1] 290763 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Cytometix Australia Pty Ltd
Address
c/o Cytometix Inc
9445 Fairway Circle
Bayside, WI 53217 USA
Country
United States of America
Secondary sponsor category [1] 289449 0
None
Name [1] 289449 0
Address [1] 289449 0
Country [1] 289449 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292394 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 292394 0
129 Glen Osmond Road, Eastwood SA 5063
Ethics committee country [1] 292394 0
Australia
Date submitted for ethics approval [1] 292394 0
19/12/2014
Approval date [1] 292394 0
18/02/2015
Ethics approval number [1] 292394 0
2014-12-714

Summary
Brief summary
This is a Phase I, randomized, double-blind, analytically masked, placebo-controlled, sequential-panel, ascending single-dose, and repeated twice daily-dose, single-center study to evaluate the safety, tolerability, pharmacokinetics and antinociceptive effects of escalating single and multiple doses of CMX-020 administered orally to healthy male and female subjects.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 54878 0
Dr Sepehr Shakib
Address 54878 0
CMAX, a division of Institute of Drug Technology (IDT) Australia Ltd, Level 5, East Wing, Royal Adelaide Hospital, North Terrace, Adelaide, SA 5000
Country 54878 0
Australia
Phone 54878 0
+61 8 8222 2763
Fax 54878 0
+61 8 8222 2907
Email 54878 0
[email protected]
Contact person for public queries
Name 54879 0
Sepehr Shakib
Address 54879 0
CMAX, a division of Institute of Drug Technology (IDT) Australia Ltd, Level 5, East Wing, Royal Adelaide Hospital, North Terrace, Adelaide, SA 5000
Country 54879 0
Australia
Phone 54879 0
+61 8 8222 2763
Fax 54879 0
+61 8 8222 2907
Email 54879 0
[email protected]
Contact person for scientific queries
Name 54880 0
Peggy Tom
Address 54880 0
Cytometix Australia Pty Ltd
c/o Cytometix Inc
9445 Fairway Circle
Bayside, WI 53217 USA
Country 54880 0
United States of America
Phone 54880 0
+1 (414) 745-8000
Fax 54880 0
Email 54880 0
[email protected]

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