KP-001 Effects in Healthy Volunteers

Overseen By Motoki Akamatsu

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Kaken Pharmaceutical

Must not be taking: Prescription medications

Disqualifiers: Cardiovascular disease, Psychiatric disorder, Drug abuse, others

Compensation: Varies

Number of Visits: 4

40 Participants Needed

Trial Summary

Do I have to stop taking my current medications for the trial?

Yes, you 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 it for treating an adverse event or if it won't interfere with the study.

What data supports the idea that KP-001 Effects in Healthy Volunteers (also known as: KP-001) is an effective treatment?

The available research shows that KRN8601, which is similar to KP-001, was effective in increasing neutrophil counts in patients with various types of chronic neutropenia. In a study with 26 patients, 23 showed increased neutrophil counts after treatment. Another study on patients with neutropenia caused by chemotherapy for lung cancer found that KRN8601 was effective in 75% of patients at a lower dose and 100% at a higher dose. This suggests that KP-001 could be effective for similar conditions. ^{1 2 3 4 5}

What safety data is available for KP-001 treatment?

The provided research does not specifically mention KP-001 or its safety data. However, it includes general safety data from various Phase I clinical trials involving healthy volunteers. These studies report on adverse events in healthy volunteers during First-in-Man trials and Phase I studies, highlighting the risks and safety considerations in such trials. The studies emphasize the importance of careful planning and execution to minimize risks, but specific data on KP-001 is not available in the provided research. ^{6 7 8 9 10}

Is the drug KP-001 a promising treatment in healthy volunteers?

The information provided does not mention KP-001, so we cannot determine if it is a promising treatment based on the given research articles. ^{11 12 13 14 15}

What is the purpose of this trial?

This is a Phase 1, single-center, randomized, single-blind (participants are blinded), placebo controlled, four-way cross over TQT study (4×4 Williams square design) to investigate the effect of KP-001 on the QTc interval using open-label moxifloxacin as an active control, in adult healthy volunteers. KP-001 and placebo (dry syrup) will be administered in blinded manner to participants, and the moxifloxacin (tablet) will be administered in open-label manner.Total duration of study participation for each participant is approximately 8 weeks. Cardiodynamic ECG evaluations will be performed at separate locations and cardiodynamic ECG evaluators will be blinded to treatment group analyzed, ie, blinded to each of the study interventions including moxifloxacin.

Eligibility Criteria

This clinical trial is for healthy adults who can participate in a study lasting about 8 weeks. Participants will be tested with KP-001, a placebo, and moxifloxacin to assess effects on heart rhythm. Specific eligibility criteria are not provided.

Inclusion Criteria

Participant is medically healthy with no clinically significant abnormal screening results (eg, medical history, physical examination, laboratory profiles, vital signs, or ECGs), in the opinion of the Investigator or designee. If screening and/or admission results are abnormal, they may be repeated once at screening and/or once at admission to confirm the participant's eligibility

My weight is at least 50 kg and my BMI is between 18 and 30.

I am not pregnant or breastfeeding and can become pregnant.

Exclusion Criteria

A resting HR of <40 bpm or >100 bpm when vital signs are measured at screening or check in

Participant has abnormal findings on the screening ECG deemed clinically significant by the Investigator or qualified designee

Participant has positive urine drug or urine alcohol and positive cotinine test results at screening or Day -1 of Treatment Period 1

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment Period 1

Participants receive a single dose of one of the study interventions and are monitored for 3 days

1 week

Residential stay from Day 1 to Day 4

Washout

Participants undergo a washout period between treatment periods

1 week

Treatment Period 2

Participants receive a single dose of one of the study interventions and are monitored for 3 days

1 week

Residential stay from Day 1 to Day 4

Washout

Participants undergo a washout period between treatment periods

1 week

Treatment Period 3

Participants receive a single dose of one of the study interventions and are monitored for 3 days

1 week

Residential stay from Day 1 to Day 4

Washout

Participants undergo a washout period between treatment periods

1 week

Treatment Period 4

Participants receive a single dose of one of the study interventions and are monitored for 3 days

1 week

Residential stay from Day 1 to Day 4

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

Treatment Details

Interventions

• KP-001

Trial Overview The trial tests the impact of KP-001 on heart rhythm compared to a placebo and moxifloxacin (a known drug). It's randomized, single-blind, uses a crossover design so everyone gets each treatment in turns.

Participant Groups

Group I: Treatment T Experimental Treatment 1 Intervention

KP-001 therapeutic dose (KP-001 100 mg + placebo)

Group II: Treatment ST Experimental Treatment 1 Intervention

KP-001 supratherapeutic dose (KP-001 400 mg)

Group III: Treatment M Active Control 1 Intervention

moxifloxacin 400 mg

Group IV: Treatment P Placebo Group 1 Intervention

placebo

Who Is Running the Clinical Trial?

Kaken Pharmaceutical

Lead Sponsor

Trials

9

Recruited

910+

Parexel

Industry Sponsor

Trials

322

Recruited

137,000+

Peyton Howell

Parexel

Chief Executive Officer

Master of Healthcare Administration from The Ohio State University, Bachelor of Arts in Health Communications from the University of Illinois

Dr. Austin Smith

Parexel

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Findings from Research

In a study of 26 patients with various forms of chronic neutropenia, KRN8601 (rhG-CSF) significantly increased neutrophil counts in 23 patients, demonstrating its efficacy as a treatment.

While KRN8601 was generally safe with no serious side effects leading to study interruption, patients with Kostmann's disease and certain other types of neutropenia showed a poorer response compared to others.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical evaluation of effects of KRN8601 (rhG-CSF) on neutropenia]. Nakahata, T., Akabane, T., Miura, A., et al.[2006]

MK-8389 was found to be generally safe and well tolerated in healthy young women over a 14-day period, although it caused transient changes in thyroid function tests that limited dose escalation above 40 mg.

While MK-8389 showed acceptable systemic exposure, it did not have a clinically meaningful effect on follicular development, although higher doses did increase inhibin B levels, indicating some early follicular activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral follicle-stimulating hormone agonist tested in healthy young women of reproductive age failed to demonstrate effect on follicular development but affected thyroid function. Gerrits, MG., Kramer, H., el Galta, R., et al.[2016]

In a rat model of cold injury, the non-competitive NMDA antagonist MK-801 significantly reduced cerebral edema and improved blood-brain barrier permeability in the penumbral zone of the lesion when administered shortly after injury.

Both MK-801 and the competitive NMDA antagonist CPP were ineffective in preventing edema accumulation at the core of the lesion, indicating that their protective effects may be limited to specific areas of brain injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protective effect of the N-methyl-D-aspartate receptor antagonists, MK-801 and CPP on cold-induced brain oedema. Görgülü, A., Kiriş, T., Unal, F., et al.[2019]

In a clinical trial involving 36 patients with chemotherapy-induced neutropenia, KRN 8601 significantly increased neutrophil counts and reduced the duration of neutropenia, showing an efficacy rate of 75% at 50 micrograms/m2 and 100% at 100 micrograms/m2.

KRN 8601 was found to be clinically effective and safe, with only mild side effects reported, including fever and slight elevations in liver enzymes in a few patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical trial of KRN 8601 in patients with neutropenia induced by chemotherapy for lung cancer]. Kimura, I., Ohonoshi, T., Okabe, T., et al.[2013]

Both KIN-804 (KIN) and KU-2285 (KU) demonstrated significant radiosensitizing effects in vitro and in vivo, with KIN showing comparable efficacy to KU across various assays, indicating their potential as effective adjuncts in radiotherapy.

The acute toxicity of KIN was assessed with an LD50/7 of 3.6 g/kg, suggesting a favorable safety profile, while pharmacokinetic studies indicated low brain uptake, which may enhance its clinical applicability by reducing central nervous system side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

KIN-804 vs. KU-2285 as a radiosensitizer for clinical use. Oya, N., Shibamoto, Y., Shibata, T., et al.[2019]

In a five-year analysis of 1,559 healthy volunteers across 142 phase I studies, the overall incidence of adverse events (AEs) was 8.8%, with most AEs being mild or moderate in severity, indicating that while AEs are common, they are generally not severe.

The incidence of AEs was significantly higher in multiple-dose studies compared to single-dose trials, highlighting the importance of study design in assessing the safety profile of active drugs, with a notable increase in AEs on the first day of drug administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events in volunteers participating in phase I clinical trials: a single-center five-year survey in 1,559 subjects. Lutfullin, A., Kuhlmann, J., Wensing, G.[2019]

The first-in-human clinical trial of BIA 10-2474 resulted in serious adverse events for 6 healthy volunteers, including 1 death, highlighting the heightened risks associated with novel investigational drugs transitioning from animal studies to human trials.

The symposium emphasized the need for careful planning and communication in clinical trials to minimize risks to participants, suggesting that a complex matrix of factors must be considered to ensure safety and integrity in first-in-human studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety in FIH Trials: A Summary of the Symposium "Fatal Drug Trial in Phase 1: Understanding Risk, Subject Safety, Timelines, and Cost". Greenberg, HE., van Iersel, MT., Westrick, ML., et al.[2020]

In a review of 109 clinical studies with 1228 healthy volunteers, 19% reported adverse events during placebo administration, highlighting that even without active treatment, participants can experience side effects.

Adverse events were more common with repeated dosing (28%) and among elderly participants (26%), with headaches, drowsiness, and asthenia being the most frequently reported issues, indicating that placebo effects can significantly influence safety evaluations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The placebo effect in healthy volunteers: influence of experimental conditions on the adverse events profile during phase I studies. Rosenzweig, P., Brohier, S., Zipfel, A.[2023]

In a review of 24 First-in-Man studies involving 1,017 healthy male volunteers, the incidence of adverse events (AEs) was low, with 98.3% of AEs being mild or moderate, indicating a favorable safety profile for small molecules in Phase I trials.

Only 0.4% of treatments resulted in serious adverse events, all of which were not medically concerning and did not require hospitalization, suggesting that small molecule trials can be conducted safely in healthy volunteers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of healthy volunteers in First-in-Man trials - an analysis of studies conducted at the Bayer in-house ward from 2000 to 2005. Wensing, G., Ighrayeb, IA., Boix, O., et al.[2019]

In a comprehensive review of 54 phase-I studies involving 1015 healthy volunteers over 10 years, the overall incidence of adverse events was found to be 12.8%, with a higher rate for active drugs (13.7%) compared to placebo (7.9%).

Most adverse events were minor, with only 3% classified as severe, and no deaths or life-threatening events reported, highlighting that while adverse events are common in phase-I trials, they are typically not serious.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events in phase-I studies: a report in 1015 healthy volunteers. Sibille, M., Deigat, N., Janin, A., et al.[2019]

In a Phase I clinical study involving 19 healthy volunteers, Ukrain was found to be well tolerated with no significant adverse effects reported, even after prolonged administration for up to three years.

The most common side effects were mild, including localized pain at the injection site, drowsiness, increased thirst, and slight changes in body temperature and blood pressure, indicating a favorable safety profile for doses ranging from 5 to 50 mg.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical studies of Ukrain in healthy volunteers (phase 1). Danysz, A., Kokoschinegg, M., Hamler, F.[2015]

In a study involving 28 healthy volunteers, SKP-450, a novel K+ channel opener, demonstrated linear pharmacokinetics and significant dose-dependent hemodynamic effects, particularly at doses of 200 and 300 micrograms.

The drug was generally well tolerated, although higher doses were associated with more frequent adverse effects like headaches, indicating a need for further evaluation of its antihypertensive efficacy in patients with high blood pressure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic/pharmacodynamic evaluation of a novel potassium channel opener, SKP-450, in healthy volunteers. Jang, IJ., Yu, KS., Shon, JH., et al.[2019]

In a double-blind randomized trial involving predominantly young healthy participants, both potassium citrate (K-cit) and potassium chloride (KCl) significantly reduced mean arterial pressure after 6 weeks, with K-cit showing a reduction of -5.22 mmHg and KCl -4.70 mmHg, indicating their efficacy in lowering blood pressure.

The study suggests that increasing dietary potassium, regardless of the form (K-cit or KCl), could help manage blood pressure levels, especially in individuals with higher baseline systolic blood pressure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of a dietary supplement of potassium chloride or potassium citrate on blood pressure in predominantly normotensive volunteers. Braschi, A., Naismith, DJ.[2013]

KATP openers have been shown to provide protective effects on the heart during ischemia by conserving myocardial energy and improving contractile function, independent of their vasodilator effects, based on in vitro studies.

In vivo studies have yielded mixed results regarding the efficacy of KATP openers, with some showing benefits in canine models of heart injury, suggesting that further research is needed to clarify their mechanisms and optimize their use for cardiac protection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protective effects of ATP-sensitive potassium-channel openers in experimental myocardial ischemia. Grover, GJ.[2017]

In a study of 38 healthy families over 4 weeks, increasing dietary potassium intake significantly raised urinary potassium excretion but did not lead to any changes in blood pressure measurements (systolic, diastolic, or mean arterial).

The study suggests that for healthy individuals with normal blood pressure, simply increasing potassium intake is unlikely to affect blood pressure levels, even though children's height and weight increased during the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blood pressure response to potassium supplementation in normotensive adults and children. Miller, JZ., Weinberger, MH., Christian, JC.[2019]

References

1. Japan pubmed.ncbi.nlm.nih.gov

[Clinical evaluation of effects of KRN8601 (rhG-CSF) on neutropenia]. [2006]

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

Oral follicle-stimulating hormone agonist tested in healthy young women of reproductive age failed to demonstrate effect on follicular development but affected thyroid function. [2016]

3. Austria pubmed.ncbi.nlm.nih.gov

Protective effect of the N-methyl-D-aspartate receptor antagonists, MK-801 and CPP on cold-induced brain oedema. [2019]

4. Japan pubmed.ncbi.nlm.nih.gov

[Clinical trial of KRN 8601 in patients with neutropenia induced by chemotherapy for lung cancer]. [2013]

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

KIN-804 vs. KU-2285 as a radiosensitizer for clinical use. [2019]

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

Adverse events in volunteers participating in phase I clinical trials: a single-center five-year survey in 1,559 subjects. [2019]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Safety in FIH Trials: A Summary of the Symposium "Fatal Drug Trial in Phase 1: Understanding Risk, Subject Safety, Timelines, and Cost". [2020]

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

The placebo effect in healthy volunteers: influence of experimental conditions on the adverse events profile during phase I studies. [2023]

9. Germany pubmed.ncbi.nlm.nih.gov

The safety of healthy volunteers in First-in-Man trials - an analysis of studies conducted at the Bayer in-house ward from 2000 to 2005. [2019]

10. Germany pubmed.ncbi.nlm.nih.gov

Adverse events in phase-I studies: a report in 1015 healthy volunteers. [2019]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical studies of Ukrain in healthy volunteers (phase 1). [2015]

12. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetic/pharmacodynamic evaluation of a novel potassium channel opener, SKP-450, in healthy volunteers. [2019]

13. England pubmed.ncbi.nlm.nih.gov

The effect of a dietary supplement of potassium chloride or potassium citrate on blood pressure in predominantly normotensive volunteers. [2013]

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

Protective effects of ATP-sensitive potassium-channel openers in experimental myocardial ischemia. [2017]

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

Blood pressure response to potassium supplementation in normotensive adults and children. [2019]