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Table 2 Summary of study procedures

From: A randomised placebo-controlled, double-blind phase II study to explore the safety, efficacy, and pharmacokinetics of sonlicromanol in children with genetically confirmed mitochondrial disease and motor symptoms (“KHENERGYC”)

Study Period

Screening

Adaptive PK study

Double-blind Treatment Period

Follow up

Timing (weeks)

−4 to −1

Day 1

Day 4

2 (pre-dose) – 27

27–29

Window (days)

+/−7 (except +7 for V7)

+/− 2

Visit number

V1

V2

V3

V4a

V5

V6

V7b

V8

Day/Week

−4 to −1

Day 1

Day 4

Wk 2 / Day 1

Wk 6

Wk 13

Wk 27

Wk 29

Informed Consent

x

       

Inclusion/Exclusion criteria

x

x

 

x

    

Demographics

x

  

xc

    

Medical history

x

x

 

xc

    

Laboratoryd

x

 

x

xe

x

x

x

x

Pregnancy testf

x

x

x

x

Monthly

Physical examination

x

  

x

x

x

x

x

Bodyweight and heightg

x

  

x

xh

xh

x

 

Vital signsi

x

x

xg

x

x

x

x

x

ECGk

x

xj

xj

x

x

x

x

x

2D-Echocardiographyl

x

     

x

 

GMFM-88

x

  

x

x

x

x

x

IPMDS

x

  

x

x

x

x

x

Study medication

 

Daily

Randomisation

   

xm

    

PEDI-CAT

   

xm

x

x

x

x

BAD

   

xm

x

x

x

x

Tardieu Spasticity test

   

xm

x

x

x

x

SARA

   

xm

x

x

x

x

9 Hole Peg Test

xn

  

xm

x

x

x

x

10 MWT

   

xm

x

x

x

x

Zarit-12 Burden scale

   

xm

x

x

x

x

NeuroQL-SF

   

xm

x

x

x

x

Clinician-scored and Patient/Caregiver scored GIC, MBSAo

   

x

x

x

x

x

EQ-5D-Y

   

xm

x

x

x

x

Health Utilities Index

   

xm

x

x

x

x

Palatability

 

x

      

Acceptability

 

Continuously

 

PK samplingp

 

x

x

   

x

 

Telephone compliance Checksq

    

Weekly

AE recording

 

Continuously

Concomitant medication

 

Continuously

Diaryr

 

Continuously

Study medication dispensing

 

x

 

x

x

x

  

Return study medication and Drug accountability

  

x

 

x

x

x

 
  1. aVisit not earlier than 10 days after the last dose in the adaptive PK study phase to avoid carry-over effects
  2. bAssessments are also to be performed in case of premature discontinuation
  3. cDemographics, Medical history on V4 only for patients not participating in the Adaptive PK study
  4. dIncluding haematology and clinical chemistry parameters. Metabolomics and biomarkers in plasma and urine (overnight sampled portion or first-morning urine portion to be collected before early morning food/drinks intake) at V4 and V7. For patients with heteroplasmic mitochondrial DNA mutations: mtDNA heteroplasmy assessment in urine at V4 and V7
  5. eOnly for patients with heteroplasmic mitochondrial DNA mutations: mtDNA heteroplasmy assessment in urine at V4
  6. fIn females with childbearing potential only, as defined in section 3.2.9. Pregnancy blood test at screening, urine (dipstick) tests at monthly intervals, and at the Follow-up visit. Females of childbearing potential will be provided with urine (dipstick) pregnancy tests and will be instructed to perform the pregnancy tests at home, at monthly intervals throughout the double-blind study treatment period. The female subjects (or parent/caregiver) will be contacted by the study staff each month to report the results of the pregnancy tests
  7. gFor subjects <3 years: height, weight, skull circumference, and weight-for-height will be assessed. For subjects>3 years, weight, height, and BMI will be assessed
  8. hBodyweight only
  9. iIncluding supine blood pressure and heart rate. Vital signs are to be recorded as close as possible to each PK assessment at V2, 3, and 7
  10. jAs close as possible before each sampling timepoint of the PK assessment
  11. kECGs will be recorded at Screening, Day 1 (V2) before first dosing on day 1; on Day 4 (V3) and Visit 7 just before the PK sample assessments; at day 1 (V4), at month 1 (V5), month 3 (V6), at month 6 (V7, just before the PK sample assessments) and Follow-up (V8)
  12. lNot to be done if documented (favourable) result dated less than 6 months prior to screening is available
  13. mBefore trial, medication intake
  14. nThis is a training session to reduce the learning effect. By conducting the learning session at the screening visit, the testing burden at V4 is reduced
  15. oThis includes the Patient / Caregiver scored global impression of change for the patient/caregiver chosen 3 most bothersome symptoms. Patient scored global impression of change to be assessed by parent/caregiver for all children under 12 years of age and children aged 12–18 considered unable to provide a reliable assessment. A baseline situation is recorded to document the most important signs and symptoms to base the impression of change
  16. pOn days 1 and 4 and Visit 7, the PK sampling schedule depends on age
  17. qTelephone contacts will be conducted starting from Day 1 of the double-blind treatment period to verify the subject’s compliance with medication intake and the correct completion of the daily diaries. In addition, female subjects of childbearing potential and/or parent/caregiver will be contacted each month and asked to report the results of the urine (dipstick) pregnancy tests to confirm the absence of pregnancy
  18. rParent/caregiver of the subject will keep a diary during the study, for daily recording of intake of study medication, including seizures, migraine frequency
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BMC Neurology

ISSN: 1471-2377

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