A Bioequivalence Study to Compare the Pharmacokinetics of Two Formulations of Siklos® in Healthy Volunteers

This study is a Phase I, open-label, single-centre, randomised, two-period, single-dose crossover study to compare and assess the bioequivalence, safety, tolerability and pharmacokinetics of hydroxycarbamide dispersible tablets (20 x 50 mg) (test IMP) and Siklos® film-coated tablet (1000 mg) (reference IMP) following single-dose administration. Thirty (30) healthy male and female participants, between 18 and 50 years of age are planned to participate in the study.

Study participants will be randomised to one of the 2 possible combination sequences. After each treatment administration, blood samples will be collected at specific time points to assess the Pharmacokinetics (PK) parameters.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Hydroxycarbamide dispersible tablets; Drug: Hydroxycarbamide film-coated tablet

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Merthyr Tydfil, United Kingdom
    • Simbec-Orion Clinical Pharmacology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy male and female participants, between 18 and 50 years of age, inclusive.
2. Female participant of childbearing potential willing to use a highly effective method of contraception, if applicable from the first dose until 3 months after the last dose of IMP.
3. Female participant of non-childbearing potential. For the purposes of this study, this is defined as the participant being amenorrhoeic for at least 12 consecutive months or at least 4 months post-surgical sterilisation.
4. Female participant with a negative pregnancy test at Screening.
5. Male participant (and partner of child bearing potential) willing to use a highly method of contraception, if applicable from first dose until 3 months after last dose of IMP.
6. Participant with a BMI of 18-29.9 kg/m2.
7. No clinically significant history of previous allergy / sensitivity to hydroxycarbamide or any of the excipients contained within the IMP(s).
8. No clinically significant abnormal test results for serum biochemistry, haematology and/or urine analyses within 28 days before the first dose administration of the IMP.
9. Participant with a negative urinary DOA screen (including alcohol) test results, determined within 28 days before the first dose administration of the IMP.
10. Participant with negative human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) and hepatitis C virus antibody (HCV Ab) test results at Screening.
11. No clinically significant abnormalities in 12-lead ECG determined within 28 days before the first dose of IMP.
12. No clinically significant abnormalities in vital signs determined within 28 days before the first dose of IMP.
13. Participant must be available to complete the study.
14. Participant must satisfy an Investigator about his/her fitness to participate in the study.
15. Participant must provide written informed consent to participate in the study.

Exclusion Criteria:

1. A clinically significant history of gastrointestinal disorder likely to influence IMP absorption.
2. Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements within 28 days or 5 half-lives prior to the first dose of IMP.
3. Evidence of renal, hepatic, central nervous system, respiratory, cardiovascular, or metabolic dysfunction.
4. A clinically significant history of drug or alcohol abuse within the past two years.
5. Inability to communicate well with the Investigators.
6. Participation in a New Chemical Entity clinical study within the previous 3 months or five half-lives whichever is the longest, or a marketed drug clinical study within the 30 days or five half-lives whichever is the longest, before the first dose of IMP.
7. Donation of 450 mL or more blood within the 3 months before the first dose of IMP.
8. Users of nicotine products i.e., current smokers or ex-smokers who have smoked within 6 months prior to Screening or users of cigarette replacements
9. Female participants who are pregnant, breastfeeding or lactating.
10. Participants who have received any live or attenuated vaccine within 28 days of the first dose of IMP, or who are planning to receive a vaccine up to 28 days after receiving the last dose of IMP in Treatment Period 2.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Test IMP; Hydroxycarbamide dispersible tablets (20 x 50 mg)	Drug: Hydroxycarbamide dispersible tablets; Hydroxycarbamide dispersible tablets (20 x 50 mg); Drug: Hydroxycarbamide film-coated tablet; Hydroxycarbamide film-coated tablet (1000 mg)
ACTIVE_COMPARATOR: Reference IMP; Hydroxycarbamide film-coated tablet (1000 mg)	Drug: Hydroxycarbamide dispersible tablets; Hydroxycarbamide dispersible tablets (20 x 50 mg); Drug: Hydroxycarbamide film-coated tablet; Hydroxycarbamide film-coated tablet (1000 mg)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	The observed maximum concentration (Cmax) in plasma	24 hours
AUC0-t	The area under the plasma concentration-time curve from time zero (pre-dose) to the time of last quantifiable concentration (t)	24 hours
AUC0-infinity	The AUC from time 0 to infinity	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
tmax	The time at which Cmax is apparent	24 hours
t1/2	The terminal elimination half-life	24 hours
ke	The terminal elimination rate-constant	24 hours
AUC%extra	% of AUC0-infinity extrapolated	24 hours
Adverse events	Incidence of Adverse Events	24 hours

Collaborators and Investigators

• Sponsor: ADDMEDICA SASA
• Collaborators: Simbec-Orion Group; PhinC Development; Oncodesign SA
• Investigators: Principal Investigator: Annelize Koch, MD, Simbec-Orion Group

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 22, 2021
• Primary Completion (ACTUAL): September 29, 2021
• Study Completion (ACTUAL): September 29, 2021

Study Registration Dates

• First Submitted: August 5, 2021
• First Submitted That Met QC Criteria: August 23, 2021
• First Posted (ACTUAL): August 27, 2021

Study Record Updates

• Last Update Posted (ACTUAL): October 7, 2021
• Last Update Submitted That Met QC Criteria: October 6, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Hydroxyurea; Hydroxycarbamide
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Antisickling Agents; Hydroxyurea
• Other Study ID Numbers: SIK-FR-21-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No