A Study to Assess the Pharmacokinetics of Sorafenib in Mesoporous Magnesium Carbonate (DPH001) Compared to Nexavar® (sorafenib) in Healthy Volunteers

NCT06797427 | Completed Early Phase 1

• 2 other identifiers: DPH001-012024-514496-18
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The study aims to assess the pharmacokinetics and safety of DPH001, an amorphous formulation of sorafenib, compared to Nexavar® in healthy volunteers.

Conditions

Healthy

Keywords

PK study; Sorafenib; Hepatocellular carcinoma; MMC; Amorphous formulation; Mesoporous magnesium carbonate; Absorption; Bioavailability; Drug delivery; Kinase inhibitors

Outcome Measures

Primary Outcomes (5)

• To compare the AUC (0-6h) of sorafenib after the administration of 100 mg DPH001 vs. 200 mg Nexavar® in fasted conditions.

  Blood samples will be collected in order to calculate a PK-profile. Area under the plasma concentration vs. time curve (AUC) from time 0 to 6 hours (AUC0 6h).

  From administration of study drug until 4 days

• To compare the AUC (0-72 h) of sorafenib after the administration of 100 mg DPH001 vs. 200 mg Nexavar® in fasted conditions.

  Blood samples will be collected in order to calculate a PK-profile. Area under the plasma concentration vs. time curve (AUC) from time 0 to 72 hours (AUC 0-72h).

  From administration of study drug until 4 days

• To compare the AUC (inf) of sorafenib after the administration of 100 mg DPH001 vs. 200 mg Nexavar® in fasted conditions.

  Blood samples will be collected in order to calculate a PK-profile. Area under the plasma concentration vs. time curve (AUC) from time 0 extrapolated to infinity (AUCinf).

  From administration of study drug until 4 days

• To compare the Cmax of sorafenib after the administration of 100 mg DPH001 vs. 200 mg Nexavar® in fasted conditions.

  Blood samples will be collected in order to calculate a PK-profile. Maximum observed plasma concentration (Cmax).

  From administration of study drug until 4 days

• To compare the Tmax of sorafenib after the administration of 100 mg DPH001 vs. 200 mg Nexavar® in fasted conditions.

  Blood samples will be collected in order to calculate a PK-profile. Time to Cmax (Tmax).

  From administration of study drug until 4 days

Secondary Outcomes (34)

• Number of subjects with treatment-related adverse events assessed by frequency.

  From administration of study drug until end of trial (period 2 day 8).

• Number of subjects with treatment-related adverse events assessed by seriouness.

  From administration of study drug until end of trial (period 2 day 8).

• Number of subjects with treatment-related adverse events assessed by intensity.

  From administration of study drug until end of trial (period 2 day 8).

• Number of subjects with treatment-related adverse events assessed by relationship to study treatment.

  From administration of study drug until end of trial (period 2 day 8).

• Number of subjects with a clinical significant change from baseline in the systolic blood pressure.

  From administration of study drug until end of trial (period 2 day 8).

Study Arms (2)

Single dose of Nexavar sorafenib

ACTIVE COMPARATOR

1 dose of 200 mg sorafenib as Nexavar®, film-coated tablets for oral administration, in a fasted state. IMP administrations (dosing) will be separated by wash-out periods of at least 14 days

Drug: Nexavar (Sorafenib)

Singel dose of DPH001

EXPERIMENTAL

1 dose of 100 mg sorafenib as DPH001, HPMC capsuls for oral administration, in a fasted state. IMP administrations (dosing) will be separated by wash-out periods of at least 14 days

Drug: DPH001

Interventions

DPH001 DRUG

100 mg

Singel dose of DPH001

Nexavar (Sorafenib) DRUG

200 mg

Single dose of Nexavar sorafenib

Eligibility Criteria

• Age: 18 Years - 65 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to give written informed consent for participation in the trial, including consenting to the planned restrictions during the trial.
• Healthy male or female participant aged 18 to 65 years, inclusive.
• Body mass index (BMI) ≥18.5 and ≤30.0 kg/m2 at the time of the screening visit.
• Medically healthy participant without abnormal clinically significant medical/surgical history, physical findings, vital signs, ECG, and laboratory values at the time of the screening visit, as judged by the Investigator.
• Female trial participants: Only female participants of non-childbearing potential will be considered eligible for participation. Female participants of non-childbearing potential are defined as:
• pre menopausal females who have undergone hysterectomy and/or bilateral salpingectomy and/or bilateral oophorectomy,
• post menopausal females, defined as having undergone at least 12 months of amenorrhea. In questionable cases a blood sample with detection of follicle stimulating hormone (FSH) \>25 IU/L will be confirmatory.
• Male trial participants: Male participants must be willing to use condoms during sexual intercourse to prevent pregnancy and/or the drug exposure of a partner from the first IMP administration at Visit 2 and until 3 months after the last IMP administration at Visit 12.
• In addition, any female partner of a male participant who is of childbearing potential must use contraceptive methods with a failure rate of \<1%/year to prevent pregnancy from at least 2 weeks prior to the first administration of IMP to 3 months after the last administration of IMP.
• The following are considered highly effective methods of contraception:
• combined (oestrogen and progestogen-containing) or progestogen-only hormonal contraception associated with the inhibition of ovulation (oral, transdermal, intravaginal, injectable, or implantable),
• intrauterine device (IUD) or intrauterine hormone-releasing system (IUS).

You may not qualify if:

• History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the participant at risk because of participation in the trial, or influence the results or the participant's ability to participate in the trial.
• Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the (first) administration of IMP.
• Malignancy within the past 5 years, with the exception of in situ removal of basal cell carcinoma.
• Any planned major surgery within the duration of the trial.
• Any positive result at the screening visit for serum hepatitis B surface antigen, hepatitis C antibodies and/or HIV antigen and antibodies.
• After 10 minutes supine rest at the screening visit, any vital signs values outside the following ranges:
• systolic blood pressure: \<90 or ≥140 mmHg, or
• diastolic blood pressure \<50 or ≥90 mmHg, or
• pulse \<40 or ≥90 bpm.
• A mean QTcF interval of ≥450 ms at screening or a family history of long QT syndrome, as judged by the Investigator.
• Abnormal ECG morphology at screening, including abnormality in PR and/or QRS intervals, as well as signs of bundle branch block (BBB), as judged by the Investigator.
• History of cardiac arrhythmias or palpitations, including ectopic heart beats and/or extra systoles (premature ventricular contractions), as judged by the Investigator.
• Hepatic dysfunction, defined as serum transaminase (aspartate aminotransferase \[AST\] and/or alanine aminotransferase \[ALT\]) levels above the upper limit of normal (ULN) at screening, if considered clinically significant by the Investigator.
• Any other clinically relevant abnormalities in clinical chemistry, haematology, and coagulation parameters from safety laboratory tests at screening, at the discretion of the Investigator.
• History of severe reaction, including allergy/hypersensitivity, to drugs with a similar chemical structure, class, or mechanism of action to sorafenib, and/or reaction to any drug that led to significant morbidity, as judged by the Investigator.

Sponsors & Collaborators

• Disruptive Pharma: lead
• CTC Clinical Trial Consultants AB: collaborator

Study Sites (1)

Clinical Trial Consultants (CTC), Dag Hammarskjölds väg 10B

Uppsala, 752 37, Sweden

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Sorafenib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Björn Schultze, MD

  Clinical Trial Consultants (CTC), Dag Hammarskjölds väg 10B, 752 37 Uppsala, Sweden

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 22, 2025
• First Posted: January 28, 2025
• Study Start: February 10, 2025
• Primary Completion: March 10, 2025
• Study Completion: March 10, 2025
• Last Updated: March 17, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)