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The purpose of this study is to determine the Effects of KP-001 on Metformin (a substrate of MATE1) and Midazolam (a substrate of CYP3A4) Pharmacokinetics and the Effect of Clarithromycin (potent CYP3A4/P-gp Inhibitor) on KP-001 Pharmacokinetics in Healthy Adult Participants. The study will also evaluate the safety and tolerability of KP-001 with and without a single dose or multiple doses of an interaction drug. The study comprises 3 parts. Participants will stay in the Clinical Unit during the study, depending on which part they assigned to. Participants will remain at the clinical site for a 13 day/12 night in-house stay (Part 1), a 14 day/13 night in house stay (Part 2), or a 11 day/10 night in-house stay (Part 3).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| KP-001/Metformin | Experimental |
| |
| KP-001/Midazolam | Experimental |
| |
| KP-001/Clarithromycin | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| KP-001 | Drug | KP-001 |
|
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetic (PK) parameters of metformin in plasma: Area under the concentration-time curve from time 0 extrapolated to infinite time (AUCinf) | To assess the effect of repeated doses of KP-001, an inhibitor of organic cation transporter 2 (OCT2) and multidrug and toxin extrusion protein 1 (MATE-1), on the PK of a single dose of metformin in healthy adult, non-east Asian participants in the United States. | 13 days |
| PK parameters of midazolam in plasma: AUCinf | To assess the effect of repeated dose of KP-001, an inducer of CYP3A4, on the PK of a single dose of midazolam in healthy adult, non-east Asian participants in the United States. | 14 days |
| PK parameters of KP-001 in plasma: AUCinf | To compare the PK of KP-001 administered alone as a single dose and in combination with clarithromycin, an inhibitor of CYP3A4 and P-gp, in healthy adult, non-east Asian participants in the United States. | 11 days |
| PK parameters of metformin in plasma: Maximum observed concentration (Cmax) | To assess the effect of repeated doses of KP-001, an inhibitor of organic cation transporter 2 (OCT2) and multidrug and toxin extrusion protein 1 (MATE-1), on the PK of a single dose of metformin in healthy adult, non-east Asian participants in the United States. | 13 days |
| PK parameters of midazolam in plasma: Cmax | To assess the effect of repeated dose of KP-001, an inducer of CYP3A4, on the PK of a single dose of midazolam in healthy adult, non-east Asian participants in the United States. | 14 days |
| PK parameters of KP-001 in plasma: Cmax |
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Inclusion Criteria:
Participant voluntarily agrees to participate in this study and signs an Institutional Review Board (IRB)-approved informed consent prior to performing any of the Screening Visit procedures.
Participants who are male or female, 18-55 years of age, inclusive, at screening.
Participant is a continuous non-smoker who has not used nicotine-containing products for at least 3 months prior to Day -1 of Treatment Period 1 and throughout the study, based on participant self-reporting and the result of cotinine test at screening and/or Day -1 of Treatment Period.
Participant is medically healthy with no clinically significant abnormal screening results (e.g., 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.
Participant has body weight ≥ 50.0 kg and BMI within the range 18.0 to 30.0 kg/m2 (inclusive) at screening.
Participant is a woman of non-childbearing potential who:
Is postmenopausal with amenorrhea for at least 1 year prior to screening and with follicle-stimulating hormone (FSH) of 40 IU/L or higher.
OR
Has undergone one of the following:
Male participant who is sexually active with female partner(s) of childbearing potential must agree to use both a condom and spermicide from the first dose until 91 days after the last dose of KP-001.
Male participant must agree not to donate sperm from the first dose until 91 days after the last dose of KP-001.
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Parexel Early Phase Clinical Unit - Los Angeles | Glendale | California | 91206 | United States |
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| Metformin | Drug | oral dose of 850 mg Metformin |
|
| Midazolam | Drug | oral dose of 2 mg Midazolam |
|
| Clarithromycin | Drug | oral doses of 1000 mg Clarithromycin |
|
To compare the PK of KP-001 administered alone as a single dose and in combination with clarithromycin, an inhibitor of CYP3A4 and P-gp, in healthy adult, non-east Asian participants in the United States. |
| 11 days |
| ID | Term |
|---|---|
| D008687 | Metformin |
| D008874 | Midazolam |
| D017291 | Clarithromycin |
| ID | Term |
|---|---|
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D004917 | Erythromycin |
| D018942 | Macrolides |
| D061065 | Polyketides |
| D007783 | Lactones |
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