SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT03351699

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

A Single-Dose Clinical Trial to Study the Safety, Tolerability, Pharmacokinetics, and Anti-Retroviral Activity of MK-4250 Monotherapy in Anti-Retroviral Therapy (ART)-Naive, HIV-1 Infected Subjects

The study will evaluate the safety, tolerability, pharmacokinetics, and anti-retroviral activity of MK-4250 monotherapy in anti-retroviral therapy (ART)-naïve, HIV-1 infected participants. The primary hypothesis of the study is that at a dose that is sufficiently safe and generally well tolerated, MK-4250 has superior antiretroviral activity compared to a historical placebo, as measured by change from baseline in plasma HIV-1 ribonucleic acid (RNA) (log10 copies/mL) at 168 hours postdose.

NCT03351699 HIV-1 Infection
MeSH: Acquired Immunodeficiency Syndrome HIV Infections

1 Interventions

Name: MK-4250

Description: MK-4250 tablets for oral administration

Type: Drug

Panel A: MK-4250 150 mg Panel B: MK-4250 600 mg Panel D: MK-4250 900 mg Panel E: MK-4250 ≤900 mg with a Low-fat Meal Panel F: MK-4250 ≤900 mg with a Moderate-fat Meal


Primary Outcomes

Description: Plasma HIV-1 RNA will be measured. The change from Baseline in plasma HIV-1 RNA (log10 copies/mL) in participants administered MK-4250 will be compared with historical placebo data.

Measure: Plasma HIV-1 RNA

Time: Day 7

Description: The percentage of participants with one or more adverse events will be assessed.

Measure: Adverse Events

Time: Up to Day 17

Description: The percentage of participants discontinued from the study due to an adverse event will be assessed.

Measure: Study Discontinuations due to an Adverse Event

Time: Up to Day 17

Secondary Outcomes

Description: Plasma will be collected for the determination of the area under the concentration-time curve up to the last measurable concentration (AUC0-last) of MK-4250.

Measure: Area Under the Concentration-Time Curve (AUC0-last) of MK-4250

Time: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, and 240 hours after administration of MK-4250.

Description: Plasma will be collected for the determination of the area under the concentration-time curve extrapolated to infinity (AUC0-inf) of MK-4250.

Measure: Area Under the Concentration-Time Curve (AUC0-inf) of MK-4250

Time: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, and 240 hours after administration of MK-4250.

Description: Plasma will be collected for the determination of the area under the concentration-time curve up to 168 hours (AUC0-168) of MK-4250.

Measure: Area Under the Concentration-Time Curve (AUC0-168) of MK-4250

Time: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, and 168 hours after administration of MK-4250.

Description: Plasma will be collected for the determination of the maximum concentration (Cmax) of MK-4250.

Measure: Maximum Concentration (Cmax) of MK-4250

Time: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, and 240 hours after administration of MK-4250.

Description: Plasma will be collected for the determination of the concentration of MK-4250 at 168 hours postdose (C168hr).

Measure: Concentration of MK-4250 at 168 Hours (C168hr)

Time: 168 hours after administration of MK-4250.

Description: Plasma will be collected for the determination of the apparent terminal half-life (t1/2) of MK-4250.

Measure: Apparent Terminal Half-life (t1/2) of MK-4250

Time: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, and 240 hours after administration of MK-4250.

Description: Plasma will be collected for the determination of the clearance (CL/F) of MK-4250.

Measure: Clearance (CL/F) of MK-4250

Time: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, and 240 hours after administration of MK-4250.

Description: Plasma will be collected for the determination of the volume of distribution (Vz/F) of MK-4250.

Measure: Volume of Distribution (Vz/F) of MK-4250

Time: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, and 240 hours after administration of MK-4250.

Purpose: Treatment

Allocation: Non-Randomized

Sequential Assignment


There are 5 SNPs

SNPs


1 E92Q

- No evidence at screening for mutations (e.g., E92Q, N55H, Q148K, Q148R and Y143R) affecting susceptibility to Integrase Strand Transfer Inhibitors (InSTIs) - Diagnosed with HIV-1 infection ≥ 3 months prior to screening or confirmed chronic HIV infection - Screening plasma Cluster of Differentiation (CD) 4+ T cell count of >200/mm^3 - Screening plasma HIV-1 RNA ≥5,000 copies/mL within 30 days prior to the treatment phase of this study - Anti-retroviral therapy (ART)-naïve, which is defined as having never received any antiretroviral agent OR ≤30 consecutive days of an investigational antiretroviral agent which is not an InSTI and no exposure to such an investigational antiretroviral agent within 60 days prior to screening OR ≤60 consecutive days of combination ART which does not include an InSTI and no exposure to such ART within 60 days prior to screening - Never received any InSTI - Willing to receive no other ART for the duration of the treatment phase of this study - Body Mass Index (BMI) ≤35 kg/m^2 - Other than HIV infection, have baseline health judged to be stable Exclusion Criteria: - Mentally or legally institutionalized / incapacitated, or significant emotional problems at the time of pretrial (screening) visit or expected during the conduct of the trial or has a history of clinically significant psychiatric disorder within the last 5 years - History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological (outside of HIV-1 infection), renal, respiratory, genitourinary or major neurological abnormalities or diseases - History of cancer (malignancy). --- E92Q ---


2 N55H

- No evidence at screening for mutations (e.g., E92Q, N55H, Q148K, Q148R and Y143R) affecting susceptibility to Integrase Strand Transfer Inhibitors (InSTIs) - Diagnosed with HIV-1 infection ≥ 3 months prior to screening or confirmed chronic HIV infection - Screening plasma Cluster of Differentiation (CD) 4+ T cell count of >200/mm^3 - Screening plasma HIV-1 RNA ≥5,000 copies/mL within 30 days prior to the treatment phase of this study - Anti-retroviral therapy (ART)-naïve, which is defined as having never received any antiretroviral agent OR ≤30 consecutive days of an investigational antiretroviral agent which is not an InSTI and no exposure to such an investigational antiretroviral agent within 60 days prior to screening OR ≤60 consecutive days of combination ART which does not include an InSTI and no exposure to such ART within 60 days prior to screening - Never received any InSTI - Willing to receive no other ART for the duration of the treatment phase of this study - Body Mass Index (BMI) ≤35 kg/m^2 - Other than HIV infection, have baseline health judged to be stable Exclusion Criteria: - Mentally or legally institutionalized / incapacitated, or significant emotional problems at the time of pretrial (screening) visit or expected during the conduct of the trial or has a history of clinically significant psychiatric disorder within the last 5 years - History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological (outside of HIV-1 infection), renal, respiratory, genitourinary or major neurological abnormalities or diseases - History of cancer (malignancy). --- E92Q --- --- N55H ---


3 Q148K

- No evidence at screening for mutations (e.g., E92Q, N55H, Q148K, Q148R and Y143R) affecting susceptibility to Integrase Strand Transfer Inhibitors (InSTIs) - Diagnosed with HIV-1 infection ≥ 3 months prior to screening or confirmed chronic HIV infection - Screening plasma Cluster of Differentiation (CD) 4+ T cell count of >200/mm^3 - Screening plasma HIV-1 RNA ≥5,000 copies/mL within 30 days prior to the treatment phase of this study - Anti-retroviral therapy (ART)-naïve, which is defined as having never received any antiretroviral agent OR ≤30 consecutive days of an investigational antiretroviral agent which is not an InSTI and no exposure to such an investigational antiretroviral agent within 60 days prior to screening OR ≤60 consecutive days of combination ART which does not include an InSTI and no exposure to such ART within 60 days prior to screening - Never received any InSTI - Willing to receive no other ART for the duration of the treatment phase of this study - Body Mass Index (BMI) ≤35 kg/m^2 - Other than HIV infection, have baseline health judged to be stable Exclusion Criteria: - Mentally or legally institutionalized / incapacitated, or significant emotional problems at the time of pretrial (screening) visit or expected during the conduct of the trial or has a history of clinically significant psychiatric disorder within the last 5 years - History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological (outside of HIV-1 infection), renal, respiratory, genitourinary or major neurological abnormalities or diseases - History of cancer (malignancy). --- E92Q --- --- N55H --- --- Q148K ---


4 Q148R

- No evidence at screening for mutations (e.g., E92Q, N55H, Q148K, Q148R and Y143R) affecting susceptibility to Integrase Strand Transfer Inhibitors (InSTIs) - Diagnosed with HIV-1 infection ≥ 3 months prior to screening or confirmed chronic HIV infection - Screening plasma Cluster of Differentiation (CD) 4+ T cell count of >200/mm^3 - Screening plasma HIV-1 RNA ≥5,000 copies/mL within 30 days prior to the treatment phase of this study - Anti-retroviral therapy (ART)-naïve, which is defined as having never received any antiretroviral agent OR ≤30 consecutive days of an investigational antiretroviral agent which is not an InSTI and no exposure to such an investigational antiretroviral agent within 60 days prior to screening OR ≤60 consecutive days of combination ART which does not include an InSTI and no exposure to such ART within 60 days prior to screening - Never received any InSTI - Willing to receive no other ART for the duration of the treatment phase of this study - Body Mass Index (BMI) ≤35 kg/m^2 - Other than HIV infection, have baseline health judged to be stable Exclusion Criteria: - Mentally or legally institutionalized / incapacitated, or significant emotional problems at the time of pretrial (screening) visit or expected during the conduct of the trial or has a history of clinically significant psychiatric disorder within the last 5 years - History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological (outside of HIV-1 infection), renal, respiratory, genitourinary or major neurological abnormalities or diseases - History of cancer (malignancy). --- E92Q --- --- N55H --- --- Q148K --- --- Q148R ---


5 Y143R

- No evidence at screening for mutations (e.g., E92Q, N55H, Q148K, Q148R and Y143R) affecting susceptibility to Integrase Strand Transfer Inhibitors (InSTIs) - Diagnosed with HIV-1 infection ≥ 3 months prior to screening or confirmed chronic HIV infection - Screening plasma Cluster of Differentiation (CD) 4+ T cell count of >200/mm^3 - Screening plasma HIV-1 RNA ≥5,000 copies/mL within 30 days prior to the treatment phase of this study - Anti-retroviral therapy (ART)-naïve, which is defined as having never received any antiretroviral agent OR ≤30 consecutive days of an investigational antiretroviral agent which is not an InSTI and no exposure to such an investigational antiretroviral agent within 60 days prior to screening OR ≤60 consecutive days of combination ART which does not include an InSTI and no exposure to such ART within 60 days prior to screening - Never received any InSTI - Willing to receive no other ART for the duration of the treatment phase of this study - Body Mass Index (BMI) ≤35 kg/m^2 - Other than HIV infection, have baseline health judged to be stable Exclusion Criteria: - Mentally or legally institutionalized / incapacitated, or significant emotional problems at the time of pretrial (screening) visit or expected during the conduct of the trial or has a history of clinically significant psychiatric disorder within the last 5 years - History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological (outside of HIV-1 infection), renal, respiratory, genitourinary or major neurological abnormalities or diseases - History of cancer (malignancy). --- E92Q --- --- N55H --- --- Q148K --- --- Q148R --- --- Y143R ---



HPO Nodes