KP-001 for Drug Interaction Study

Overseen By Motoki Akamatsu

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Kaken Pharmaceutical

Must not be taking: Recreational drugs, St. John's wort

Disqualifiers: Psychiatric disorder, Drug abuse, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

Part 1 will evaluate the effects of KP-001 as an inhibitor of BCRP on the PK of rosuvastatin. In the Treatment Period 1, a single dose of rosuvastatin will be administered. In the Treatment Period 2, KP-001 will be administered once daily for 7 days and a single dose of rosuvastatin will be administered. Blood PK assessments of rosuvastatin will be performed until 48 hours postdose in each Treatment Period. Part 2 will evaluate the effects of KP-001 as an inducer and inhibitor of CYP1A2 on the PK of caffeine. A single dose of caffeine will be administered in the Treatment Period 1. KP-001 will be administered once daily for 10 days and a single dose of caffeine will be administered in the Treatment Period 2. Blood PK assessments of caffeine will be performed until 24 hours postdose in each Treatment Period. Part 3 will evaluate the effects of fluvoxamine as an inhibitor of CYP1A2 on the PK of KP-001. A single dose of KP-001 will be administered in the Treatment Period 1. Fluvoxamine will be administered as a single dose on the first day and then twice daily for 5 days and a single dose of KP-001 will be administered in the Treatment Period 2. Blood PK assessments of KP-001 will be performed until 48 hours postdose in each Treatment Period.

Do I need to stop taking my current medications to join the trial?

Yes, participants must stop taking any prescription or non-prescription medications, including vitamins and supplements, at least 14 days before the trial starts and until the follow-up call, unless the investigator approves otherwise.

Is KP-001 (Fluvoxamine) generally safe for humans?

Fluvoxamine has been used by over 8 million patients worldwide, and the rate of drug interactions is very low. Most interactions occur when taken with other medications, like antidepressants or blood thinners, and serious side effects are rare. ^{1 2 3 4 5}

What makes the drug KP-001 unique compared to other treatments?

The drug KP-001 is being studied for its interaction with fluvoxamine, an antidepressant that affects serotonin levels in the brain. This study is unique because it focuses on how KP-001 interacts with fluvoxamine, which is known for having complex interactions with other drugs, particularly those metabolized by the liver enzyme cytochrome P450 1A2. ^{2 3 5 6 7}

What data supports the effectiveness of the drug KP-001 when used with Fluvoxamine?

The research indicates that fluvoxamine can interact with other drugs, potentially increasing their levels in the body, as seen with mirtazapine. This suggests that fluvoxamine may enhance the effects of other drugs it is combined with, although specific data on KP-001 is not provided. ^{1 2 3 4 8}

Are You a Good Fit for This Trial?

Healthy volunteers aged 18-55, non-smokers for at least 3 months, with a BMI of 18.0 to 30.0 kg/m2 can join this trial. Women must not be able to bear children or be pregnant/breastfeeding; men must use contraception. Participants should have no significant health issues.

Inclusion Criteria

Medically healthy participant with no clinically significant abnormal screening results, in the opinion of the Investigator or designee

I am not pregnant, breastfeeding, and cannot become pregnant.

Participant who voluntarily agrees to participate in the study and signs an IRB-approved informed consent prior to performing any Screening Visit procedures

Exclusion Criteria

Participant with significant history or clinical manifestation of various disorders as determined by the Investigator or designee

I have no other illnesses that could affect the study or increase my risk.

I am not legally, mentally, or physically incapacitated and do not have significant mental or emotional problems.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Period 1 - Rosuvastatin

A single dose of rosuvastatin is administered and blood PK assessments are performed until 48 hours postdose

1 week

Treatment Period 2 - KP-001 and Rosuvastatin

KP-001 is administered once daily for 7 days with a single dose of rosuvastatin, followed by blood PK assessments until 48 hours postdose

2 weeks

Treatment Period 1 - Caffeine

A single dose of caffeine is administered and blood PK assessments are performed until 24 hours postdose

1 week

Treatment Period 2 - KP-001 and Caffeine

KP-001 is administered once daily for 10 days with a single dose of caffeine, followed by blood PK assessments until 24 hours postdose

2 weeks

Treatment Period 1 - KP-001

A single dose of KP-001 is administered and blood PK assessments are performed until 48 hours postdose

1 week

Treatment Period 2 - Fluvoxamine and KP-001

Fluvoxamine is administered as a single dose on the first day and then twice daily for 5 days with a single dose of KP-001, followed by blood PK assessments until 48 hours postdose

2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Fluvoxamine
• KP-001

Trial Overview The study tests KP-001's effects on the body's handling of rosuvastatin and caffeine, and fluvoxamine's effect on KP-001. It involves taking these drugs separately or together over different periods with blood tests to measure drug levels.

How Is the Trial Designed?

Group I: KP-001/Rosuvastatin calcium Experimental Treatment 2 Interventions

Group II: KP-001/Fluvoxamine Experimental Treatment 2 Interventions

Group III: KP-001/Caffeine citrate Experimental Treatment 2 Interventions

Who Is Running the Clinical Trial?

Kaken Pharmaceutical

Lead Sponsor

Trials

9

Recruited

910+

Citations

1. Germany pubmed.ncbi.nlm.nih.gov

The importance of drug-drug interactions as a cause of adverse drug reactions: a pharmacovigilance study of serotoninergic reuptake inhibitors in France. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

The potential for clinically significant drug-drug interactions involving the CYP 2D6 system: effects with fluoxetine and paroxetine versus sertraline. [2022]

3. Australia pubmed.ncbi.nlm.nih.gov

Pharmacokinetic interaction between tandospirone and fluvoxamine in the rat contextual conditioned fear stress model and its functional consequence: Involvement of cytochrome P450 3A4. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Fluvoxamine augmentation increases serum mirtazapine concentrations three- to fourfold. [2018]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Fluvoxamine. A review of global drug-drug interaction data. [2022]

6. Germany pubmed.ncbi.nlm.nih.gov

Effects of concomitant fluvoxamine on the metabolism of alprazolam in Japanese psychiatric patients: interaction with CYP2C19 mutated alleles. [2022]

7. England pubmed.ncbi.nlm.nih.gov

High performance liquid chromatography with ultraviolet detection used for laboratory routine determination of fluvoxamine in human plasma. [2017]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Sensitive one-step extraction procedure for column liquid chromatographic determination of fluvoxamine in human and rat plasma. [2019]