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Trial registered on ANZCTR

Registration number

ACTRN12615000885594

Ethics application status

Approved

Date submitted

17/07/2015

Date registered

24/08/2015

Date last updated

13/10/2016

Type of registration

Prospectively registered

Titles & IDs

Public title

A study to evaluate the safety and analgesic efficacy of oral CMX-020 in subjects with symptoms of sciatica resulting from lumbosacral radiculopathy.

Scientific title

A Randomized, Double-Blind, Placebo-Controlled Crossover Study to Evaluate the Analgesic Efficacy and Safety of Oral CMX-020 in Subjects with Symptoms of Sciatica Resulting from Lumbosacral Radiculopathy.

Secondary ID [1]

Nil

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Chronic pain

Lumbosacral radiculopathy

Condition category

Condition code

Musculoskeletal

Other muscular and skeletal disorders

Anaesthesiology

Pain management

Neurological

Other neurological disorders

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

The study will consist of a Screening Period (Pretreatment Day –28 to Day –1), a 10 day Treatment Period (Days 1-10), a 7 day Washout Period (Days 11-17), a second 10 day Treatment period (Days 18-27) and a 7 day Follow-up Period (Days 28-34). There will be six clinic visits during the course of the study; Visit 1 during Screening; Visit 2 will occur on the first Day of Treatment Period One (Day 1); Visit 3 on Day 10 at the end of Treatment Period One; Visit 4 at the start of Treatment Period Two (Day 18); Visit 5 on Day 27 at the conclusion of Treatment Period Two; and Visit 6 at the end of the Follow-up Period (Day 34) for study exit.

The interventional product, CMX-020, will be administered as an oral capsule.

CMX-020 and matching placebo will be provided as 25 mg capsules. Each dose will consist of 125 mg CMX-020/ placebo in the form of five 25 mg softgel capsules taken three times daily during the treatment periods one and two in cross-over randomised double-blinded manner.

Subjects will orally self-administer the randomised dose at home, three times per day (TID):
- in the morning (approx. 06:00 to 08:00)
- midday (approx. 12:00 to 14:00)
- evening (approx. 19:00 to 21:00)

Subjects will be instructed to take each dose with a full glass of room temperature water. Fasting will be required for one hour before until 30 minutes after the dose.

The date and time of each dose will be recorded by the patient in the Patient Daily Pain Diary.

On study Day 1 (Visit 2) and Day 18 (Visit 4), the initial dose for the treatment period will be administered at the study unit under the supervision of the study staff. This will be the midday dose (12:00 to 14:00). The later evening dose (19:00-21:00) will be self-administered by the subject at home. No morning dose will be taken on these days.

To confirm self-administration at home, the participants will be contacted by phone (verbally or text) daily to confirm medication dosing and completion of the pain diary. This will also be captured in the CRF.

On the mornings of study Day 10 and Day 27, the last dose for each of the treatments periods will be self-administered by the subject at home, before returning to the study unit for Study Visits 3 and 5, respectively. This will be the only dose administered on these study days.

During the follow-up period following the end of treatment period two; the participants will record their pain in the diary but will receive no treatment.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

The comparator/ control for this trial is oral 25 mg capsule of matching placebo. Placebo is OmeRx DHA triglycerides containing mixed tocopherols.

Control group

Placebo

Outcomes

Primary outcome [1]

1. To evaluate the efficacy of CMX-020 administered orally to male and female subjects with lumbosacral radiculopathy (sciatica) pain.

The primary efficacy endpoint will be the difference between the average of the placebo treatment and the average of the drug treatment for change in daily worst leg pain. Change in daily worst leg pain is the difference between baseline worst leg pain and worst leg pain on last full day of dosing.

Timepoint [1]

Daily pain intensity scores will be recorded in the Patient Daily Pain Diary by the subject each day of the study beginning on Day 1, with the final entry on Day 33. The NRS scale assessments needs to be completed each evening immediately prior to the evening dose of the study medication

Secondary outcome [1]

1. Change in average leg pain when comparing baseline average to last full day of dosing.

Timepoint [1]

Secondary outcome [2]

2. Quality of life as assessed by the Patient Global Impression of Change questionnaire.

Timepoint [2]

This self reported assessment will be administered to the subjects at the study unit at:
Visit 3 (Day 10), Visit 4 (Day 18), Visit 5 (Day 27) and Visit 6 (Day 34).

Secondary outcome [3]

3. Quality of life as assessed by the Oswestry Disability Index.

Timepoint [3]

This self reported assessment will be administered to the subjects at the study unit at:
Visit 2 (Day 1) - to establish baseline scores, Visit 3 (Day 10),
Visit 4 (Day 18), Visit 5 (Day 27) and Visit 6 (Day 34).

Secondary outcome [4]

4. Safety endpoints including AEs, SAEs, vital signs (BP, Pulse, RR, temperature, oxygen saturation), physical examination including body weight, clinical laboratory (hematology, clinical chemistry and urinalysis) and ECG.

Timepoint [4]

The safety assessments mentioned above are composite secondary outcome and will be done at Visit 1 (screening) - to assess eligibility, Visit 2 (Day 1) - predose to establish baseline values, Visit 3 (Day 10), Visit 4 (Day 18), Visit 5 (Day 27) and Visit 6 (Day 34).
The most common AEs from taking CMX-020 repeatedly were mild headache and nausea which had been assessed clinically. There have been no known/ possible SAEs associated with this study drug.
The BP, pulse and oxygen saturation are assessed by pulse oximetry while respiratory rate, physical examination will be assessed clinically. Temperature will be assessed by using a tympanic thermometer while an ECG will be recorded by an instrument which involves the placement of electrodes on the chest wall.
Blood will be collected for hematology and clinical chemistry lab assessments while urine will be collected for urinalysis.

Eligibility

Key inclusion criteria

- adult male or female between the ages of 18-75 years,
inclusive.
- The subject has a current diagnosis of lumbar radiculopathy with a duration of greater than 6 weeks, defined by all of the following:
i. Pain radiating into one leg in a distribution consistent with lumbar radiculopathy.
ii. Positive straight leg raise (L5, S1) or positive femoral stretch test (L3, L4).
iii. Confirmation of diagnosis by CT or MRI performed no more than 6 months before Screening Visit 1. The exam should demonstrate pathology at a location consistent with the clinical symptoms of radicular pain and nerve root irritation.
iv. Mean pain score of >4 on the 11 point NRS scale for “average leg pain over the last 24 hours” for at least 5 of 7 days prior to randomization. This score must be greater than mean “average back pain over the last 24 hours” score for the same period.
- subject must be on a stable analgesic regimen for the treatment of sciatic pain and must be willing to continue that regimen for the duration of the study.
- 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.
- negative urine toxicology screen for drugs of abuse during screening and baseline treatment period 1 visit.
- negative for hepatitis B surface antigen, hepatitis C antibody and HIV at screening visit.

Minimum age

18 Years

Maximum age

75 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

- medical history of hypertension, hypotension or postural hypotension.
- history or family history of seizure, including juvenile febrile seizure.
- history of head trauma, metabolic disorder, alcohol or drug withdrawal, or CNS infection.
- recent history of syncope.
- medical condition other than lumbar radiculopathy that is not well controlled with treatment or is deemed CS by the PI.
- diagnosis of complex regional pain syndrome, acute spinal cord compression, severe or progressive lower extremity weakness/ numbness, bowel/bladder dysfunction, back pain due to secondary infection or tumour or confirmed/suspected neoplasm.
- undergone surgical procedure for back pain will be evaluated for study eligibility on a case by case basis and may be excluded at the discretion of PI.
- received a nerve or plexus block, including epidural steroid injections or facet blocks, within 2 weeks prior to screening visit.
- radicular pain involving more than one spinal nerve.
- clinically significant abnormal ECG at screening.
- history of long QT syndrome or a QTcF interval > 450 msec at screening.
- 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.
- major psychiatric condition (e.g. major depression, schizophrenia) or who has clinically significant anxiety or depression as defined by a HADS score greater than 10.
- intolerant to oxycodone.
- received MAO inhibitors within 14 days prior to the screening visit.
- positive alcohol or drugs of abuse test at any visit (except for opioids if currently on prescribed or OTC opioids used as analgesic regimen).
- history or clinical significant disease or abnormal surgical or medical condition which might compromise gastrointestinal, hepatic, or renal function and alter the absorption, distribution, metabolism, or excretion of study drug.
- AST or ALT> twice ULN or creatinine > 1.9 mg/dl at screening or any lab abnormality which in opinion of Investigator would contraindicate study participation.
- Creatinine clearance of less than 60 mL/min during the Screening 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)

After informed consent has been obtained, all screening tests establishing subject eligibility will be performed within a period of 28 days before dosing. Subjects will be admitted to the clinical facility on Day -1.

The study population will comprise a minimum of 40, but up to 60, male and female subjects 18 to 75 years of age with current diagnosis of sciatic pain of duration more than 6 weeks.

In this study there are two treatment periods each consisting of 10 days in which subjects will be administered either CMX020 or placebo in a randomised crossover manner. Subjects will be required to consume 125 mg CMX-020/ placebo in the form of five 25 mg softgel capsules taken three times daily during the treatment period.

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).

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

Intervention assignment

Crossover

Other design features

Phase

Phase 2

Type of endpoint/s

Efficacy

Statistical methods / analysis

Primary and secondary endpoints will be analyzed using the Per Protocol Set. The ITT population will be supportive. All safety variables will be analyzed using Safety Population. Sensitivity analyses may be carried out comparing study results observed in the Per Protocol Set, Full Analysis Set, and ITT study populations.
The mean pain intensity score of the baseline and the final day of dosing, as well as the change in the mean pain intensity score between baseline and the final day of dosing will be summarized using mean, standard deviation, median and range. Confidence intervals when appropriate will be provided at 90% level for key primary efficacy and safety variables.
The primary efficacy variables will be summarized at each visit in terms of descriptive statistics by treatment.

The sample size of 40 to 60 subjects is a projection of crossover results based on the results of the parallel study Freeman 2013, where a difference of 2 units of pain scale between placebo response and active treatment response had a standard deviation of approximately 3 units of pain. For a crossover study to detect a difference of 2 units with SD of 3 units, at a 2-sided 5% significance with 80% power at least 38 subjects would be required while 50 subjects would be required for achieving 90% power.

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

28/08/2015

Actual

28/08/2015

Date of last participant enrolment

Anticipated

13/11/2015

Actual

26/04/2016

Date of last data collection

Anticipated

Actual

1/06/2016

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

Recruitment hospital [1]

The Royal Adelaide Hospital - Adelaide

Recruitment postcode(s) [1]

5000 - Adelaide

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Cytometix Inc.

Address [1]

9445 Fairway Circle
Bayside, WI 53217 USA

Country [1]

United States of America

Primary sponsor type

Commercial sector/Industry

Name

Cytometix Inc.

Address

9445 Fairway Circle
Bayside, WI 53217 USA

Country

United States of America

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Royal Adelaide Hospital HREC

Ethics committee address [1]

Level 4, Women’s Health Centre, Royal Adelaide Hospital
North Terrace, Adelaide  SA  5000

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

11/05/2015

Approval date [1]

15/06/2015

Ethics approval number [1]

HREC/15/RAH/191

Summary

Brief summary

This is a Phase IIa, randomized, double-blind, placebo-controlled crossover study to evaluate the efficacy and safety of oral CMX-020 in subjects with lumbosacral radiculopathy (sciatica).

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof Guy Ludbrook

Address

Pain and Anaesthesia Research Clinic (PARC) Clinical Research
Level 4, Ward S4A, North wing
RAH, North Terrace,
Adelaide, SA - 5000

Country

Australia

Phone

+61 8 8222 2712

Fax

+61 8 8222 2713

[email protected]

Contact person for public queries

Name

Guy Ludbrook

Address

Pain and Anaesthesia Research Clinic (PARC) Clinical Research
Level 4, Ward S4A, North wing
RAH, North Terrace,
Adelaide, SA - 5000

Country

Australia

Phone

+61 8 8222 2712

Fax

+61 8 8222 2713

[email protected]

Contact person for scientific queries

Name

Peggy Tom

Address

Cytometix Inc 9445 Fairway Circle Bayside, WI 53217 USA

Country

United States of America

Phone

+1 (414) 745-8000

Fax

[email protected]

No information has been provided regarding IPD availability

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Epoxy Fatty Acids Are Promising Targets for Treatment of Pain, Cardiovascular Disease and Other Indications Characterized by Mitochondrial Dysfunction, Endoplasmic Stress and Inflammation.	2020	https://dx.doi.org/10.1007/978-3-030-50621-6_5

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically