Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2018-003681-13 | EudraCT Number |
Not provided
Not provided
Not provided
Following an internal portfolio review, Ipsen has made the decision to terminate study D-US-60090-001. Ipsen would like to highlight that early termination was not due to any safety or tolerability issues with IPN60090
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The purpose of the protocol is to determine safety, tolerability, recommended dose (RD), pharmacokinetics (PK), pharmacodynamics (PD) and preliminary anti-tumour activity of IPN60090 as a single agent (Part A) and in combination with pembrolizumab (Part B) or paclitaxel (Part C) in patients with advanced solid tumours and to evaluate food effect (Part D).
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| IPN60090 | Experimental | Part 1: Dose escalation of IPN60090, Part 2: Dose expansion IPN60090 given as a Bis in Die (BID) oral dose administered up to Maximum Tolerated Dose (MTD) over a 21-day cycle |
|
| IPN60090 in combination with pembrolizumab | Experimental | Part 1: Dose escalation of IPN60090 in combination with pembrolizumab, Part 2: Dose expansion IPN60090 given as a Bis in Die (BID) oral dose, starting with pharmacologically active dose identified in 1dose escalation of IPN60090 as a single agent, over a 21-day cycle in combination with 200 mg pembrolizumab given every 21 days (Day 1 of every cycle) as IV infusion |
|
| IPN60090 in combination with paclitaxel | Experimental | Part 1: Dose escalation of IPN60090 in combination with paclitaxel, Part 2: Dose expansion IPN60090 given as a BID oral dose, starting with pharmacologically active dose identified in dose escalation of IPN60090 as a single agent over a 21-day cycle in combination with 175 mg/m2 or 135 mg/m2 paclitaxel given every 21 days (Day 1 of every cycle) as IV infusion |
|
| IPN60090 food effect | Experimental | Part 1: Food Effect of IPN60090 IPN60090 given as a single oral dose as a single agent at the recommended dose (RD) under fasting and fed conditions followed by IPN60090 given as a BID oral dose administered at the RD over a 21-day cycle. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| IPN60090 | Drug | Oral capsules given daily |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) in Part A | An adverse event (AE) is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a study drug, whether or not considered causally related to the study drug. An undesirable medical condition can be symptoms, signs or the abnormal results of an investigation. An SAE is any AE that: results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; results in congenital anomaly or birth defect; or is medically important. A TEAE is defined as any AE that began or worsened following the first administration of study drugs. AEs were recorded and graded according of the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0.
| TEAEs were to be collected from the start of the first dose of IPN60090 (Cycle 1 Day 1) up to 30 days after the date of the decision to permanently discontinue study treatment, assessed until data cut-off for study termination (maximum of 219 days). |
| Number of Participants With Dose-Limiting Toxicities (DLT) in Cycle 1 of Part A | The maximum tolerated dose (MTD) is defined as the maximum dose of IPN60090 administered BID for 21 days, so that no more than 30% of participants experience a DLT. The MTD was determined using a Bayesian Optimal Interval design. The DLT assessment period was the first 21 days of treatment (one cycle). | Up to Cycle 1 Day 21 of Part A |
| Recommended Dose of IPN60090 in Part A | The recommended dose was determined by the safety review committee following an ad-hoc review of the safety and tolerability data during Part A of the study. | Up to Cycle 1 Day 21 of Part A |
| Measure | Description | Time Frame |
|---|---|---|
| Best Overall Response (BOR) in Part A | The BOR is defined as the best response designation [in the order of complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD)] for each participant that is recorded between the date of the first dose of the study drug and the date of documented disease progression per RECIST 1.1 or the date of subsequent anticancer therapy whichever occurs first. Per RECIST v1.1, CR is disappearance of all target lesions; PR is >=30% decrease in the sum of the longest diameter of target lesions; and overall response = CR + PR. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Ipsen Medical Director | Ipsen | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| MD Anderson Cancer Center | Houston | Texas | 77030 | United States |
Not provided
Not provided
Not provided
Not provided
Not provided
The study was divided into 4 parts: Part A (dose escalation and dose expansion of IPN60090 monotherapy); Part B (dose escalation and dose expansion of IPN60090 + pembrolizumab); Part C (dose escalation and dose expansion of IPN60090 + paclitaxel); and Part D (food effect on IPN60090). Parts B, C and D were not performed due to study termination. A total of 22 participants received IPN60090 in Part A of the study.
This Phase 1 first in human dose escalation and dose expansion study was conducted in participants with advanced solid tumours at 1 investigational site in United States of America between 22 March 2019 and 21 December 2020. The sponsor decided to terminate the study during the dose escalation phase (Part A) of the study following an internal portfolio review.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | IPN60090 20 mg | Participants received IPN60090 20 milligram (mg) capsules orally twice daily (BID) up to Cycle 7 in Part A of the study. |
| FG001 | IPN60090 40 mg | Participants received IPN60090 40 mg capsules orally BID up to Cycle 2 in Part A of the study. |
| FG002 | IPN60090 80 mg | Participants received IPN60090 80 mg capsules orally BID up to Cycle 5 in Part A of the study. |
| FG003 | IPN60090 120 mg | Participants received IPN60090 120 mg capsules orally BID up to Cycle 9 in Part A of the study. |
| FG004 | IPN60090 180 mg | Participants received IPN60090 180 mg capsules orally BID up to Cycle 9 in Part A of the study. |
| FG005 | IPN60090 240 mg | Participants received IPN60090 240 mg capsules orally BID up to Cycle 4 in Part A of the study. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Safety population included all participants who were exposed to (or started receiving) IPN60090.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | IPN60090 20 mg | Participants received IPN60090 20 mg capsules orally BID up to Cycle 7 in Part A of the study. |
| BG001 | IPN60090 40 mg | Participants received IPN60090 40 mg capsules orally BID up to Cycle 2 in Part A of the study. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) in Part A | An adverse event (AE) is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a study drug, whether or not considered causally related to the study drug. An undesirable medical condition can be symptoms, signs or the abnormal results of an investigation. An SAE is any AE that: results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; results in congenital anomaly or birth defect; or is medically important. A TEAE is defined as any AE that began or worsened following the first administration of study drugs. AEs were recorded and graded according of the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0.
| Safety population included all participants who were exposed to (or started receiving) IPN60090. | Posted | Count of Participants | Participants | No | TEAEs were to be collected from the start of the first dose of IPN60090 (Cycle 1 Day 1) up to 30 days after the date of the decision to permanently discontinue study treatment, assessed until data cut-off for study termination (maximum of 219 days). |
TEAEs were to be collected from the start of the first dose of IPN60090 (Cycle 1 Day 1) up to 30 days after the date of the decision to permanently discontinue study treatment, assessed until data cut-off for study termination (maximum of 219 days).
Safety population included all participants who were exposed to (or started receiving) IPN60090.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | IPN60090 20 mg | Participants received IPN60090 20 mg capsules orally BID up to Cycle 7 in Part A of the study. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Vomiting | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
The study was terminated by the sponsor following an internal portfolio review during the dose escalation phase (Part A). The early termination was not due to any safety or tolerability issues with IPN60090.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | Ipsen | see email | clinical.trials@ipsen.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Dec 10, 2019 | Sep 28, 2021 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Dec 17, 2020 | Sep 28, 2021 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| C582435 | pembrolizumab |
| D017239 | Paclitaxel |
| ID | Term |
|---|---|
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| pembrolizumab | Drug | An intravenous solution in single-use vial to be diluted for infusion. |
|
| paclitaxel | Drug | An intravenous solution in single-use vial to be diluted for infusion. |
|
| IPN60090 single administration | Drug | Oral capsules given once |
|
| RECIST assessments performed at baseline (within 28 days before start of study drug), every 6 weeks +/-1 week for first 24 weeks, then every 12 weeks +/-2 weeks thereafter. Up to data cut-off for study termination (maximum of 247 days). |
| Objective Response Rate (ORR) in Part A | The ORR is defined as the percentage of participants in whom the BOR is equal to CR and PR for Part A. The BOR is defined as the best response designation (in the order of CR, PR, SD, PD) for each participant that is recorded between the date of the first dose of the study drug and the date of documented disease progression per RECIST 1.1 or the date of subsequent anticancer therapy whichever occurs first. Per RECIST v1.1, CR is disappearance of all target lesions; PR is >=30% decrease in the sum of the longest diameter of target lesions; and overall response = CR + PR. | RECIST assessments performed at baseline (within 28 days before start of study drug), every 6 weeks +/-1 week for first 24 weeks, then every 12 weeks +/-2 weeks thereafter. Up to data cut-off for study termination (maximum of 247 days). |
| Disease Control Rate (DCR) in Part A | The DCR is defined as the percentage of participants in whom the BOR is equal to CR, PR or SD for Part A. The BOR is defined as the best response designation (in the order of CR, PR, SD, PD) for each participant that is recorded between the date of the first dose of the study drug and the date of documented disease progression per RECIST 1.1 or the date of subsequent anticancer therapy whichever occurs first. Per RECIST v1.1, CR is disappearance of all target lesions; PR is >=30% decrease in the sum of the longest diameter of target lesions; and overall response = CR + PR. | RECIST assessments performed at baseline (within 28 days before start of study drug), every 6 weeks +/-1 week for first 24 weeks, then every 12 weeks +/-2 weeks thereafter. Up to data cut-off for study termination (maximum of 247 days). |
| Mean Progression Free Survival (PFS) in Part A | The PFS is defined as the time from first dose of study drug to the first documented objective disease progression (for RECIST 1.1), clinical disease progression collected at end of treatment, or death due to any cause, whichever occurred first. Per RECIST 1.1, progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. | RECIST assessments performed at baseline (within 28 days before start of study drug), every 6 weeks +/-1 week for first 24 weeks, then every 12 weeks +/-2 weeks thereafter. Up to data cut-off for study termination (maximum of 247 days). |
| Mean Overall Survival (OS) in Part A | The OS is defined as the time from first dose of study drug to death due to any cause. Participants who were lost to follow-up or who were still alive at the time of analysis is censored at the last day the participant was known to be alive or data cut-off date, whichever occurred first. | RECIST assessments performed at baseline (within 28 days before start of study drug), every 6 weeks +/-1 week for first 24 weeks, then every 12 weeks +/-2 weeks thereafter. Up to data cut-off for study termination (maximum of 247 days). |
| Mean Best Percent Change From Baseline in the Sum of Diameters of the Target Lesions at Minimum Post-Baseline in Part A | All measurable lesions up to a maximum of two lesions per organ and five lesions in total, representative of all involved organs, identified as target lesions and measured at baseline. Baseline is defined as the last measurement prior to the first dose of study drug. | Baseline (within 28 days before start of study drug) and post-baseline, up to data cut-off for study termination (maximum of 247 days). |
| Maximum Observed Concentration (Cmax) of IPN60090 in Part A | Blood samples were collected to determine Cmax of IPN60090. The pharmacokinetics (PK) of IPN60090 plasma concentrations were performed using noncompartmental analysis. | Pre-dose and 0.5, 1, 2, 4, 8 and 12 hours post-dose on Cycle 1 Day 1 and Cycle 1 Day 14 in Part A |
| Time to Reach Maximum Observed Concentration (Tmax) of IPN60090 in Part A | Blood samples were collected to determine Tmax of IPN60090. The PK of IPN60090 plasma concentrations were performed using noncompartmental analysis. | Pre-dose and 0.5, 1, 2, 4, 8 and 12 hours post-dose on Cycle 1 Day 1 and Cycle 1 Day 14 in Part A |
| Trough Plasma Concentration (Ctrough) of IPN60090 in Part A | Blood samples were collected to determine Ctrough of IPN60090. The PK of IPN60090 plasma concentrations were performed using noncompartmental analysis. | Pre-dose and 0.5, 1, 2, 4, 8 and 12 hours post-dose on Cycle 1 Day 14 in Part A |
| Area Under the Concentration Versus Time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) of IPN60090 in Part A | Blood samples were collected to determine AUC0-last of IPN60090. The PK of IPN60090 plasma concentrations were performed using noncompartmental analysis. | Pre-dose and 0.5, 1, 2, 4, 8 and 12 hours post-dose on Cycle 1 Day 1 and Cycle 1 Day 14 in Part A |
| Apparent Elimination Half-Life (T1/2) of IPN60090 in Part A | Blood samples were collected to determine T1/2 of IPN60090. The PK of IPN60090 plasma concentrations were performed using noncompartmental analysis. | Pre-dose and 0.5, 1, 2, 4, 8 and 12 hours post-dose on Cycle 1 Day 1 in Part A |
| Apparent Total Body Clearance (CL/F) of IPN60090 in Part A | Blood samples were collected to determine CL/F of IPN60090. The PK of IPN60090 plasma concentrations were performed using noncompartmental analysis. | Pre-dose and 0.5, 1, 2, 4, 8 and 12 hours post-dose on Cycle 1 Day 1 in Part A |
| Apparent Volume of Distribution (Vz/F) of IPN60090 in Part A | Blood samples were collected to determine Vz/F of IPN60090. The PK of IPN60090 plasma concentrations were performed using noncompartmental analysis. | Pre-dose and 0.5, 1, 2, 4, 8 and 12 hours post-dose on Cycle 1 Day 1 in Part A |
| Target Engagement in Part A | The target engagement is glutamate:glutamine (Glu:Gln) ratio in peripheral blood mononuclear cells. Glu:Gln ratio inhibition is calculated as (1 - post-baseline Glu:Gln ratio/Cycle 1 Day 1 predose Glu:Gln ratio) x 100%. | At 2 and 12 hours postdose on Cycle 1 Day 1; predose, 2 and 12 hours postdose on Cycle 1 Day 14; and predose, 2 and 2-4 hours postdose on Cycle 1 Day 15 in Part A |
| Withdrawal by Subject |
|
| Progressive Disease Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 |
|
| Progressive Disease Clinical |
|
| Study termination by sponsor |
|
| BG002 | IPN60090 80 mg | Participants received IPN60090 80 mg capsules orally BID up to Cycle 5 in Part A of the study. |
| BG003 | IPN60090 120 mg | Participants received IPN60090 120 mg capsules orally BID up to Cycle 9 in Part A of the study. |
| BG004 | IPN60090 180 mg | Participants received IPN60090 180 mg capsules orally BID up to Cycle 9 in Part A of the study. |
| BG005 | IPN60090 240 mg | Participants received IPN60090 240 mg capsules orally BID up to Cycle 4 in Part A of the study. |
| BG006 | Total | Total of all reporting groups |
| years |
|
| Age, Customized | Count of Participants | Participants | No |
|
| Sex: Female, Male | Count of Participants | Participants | No |
|
| Race/Ethnicity, Customized | Count of Participants | Participants | No |
|
| Race/Ethnicity, Customized | Count of Participants | Participants | No |
|
|
|
|
| Primary | Number of Participants With Dose-Limiting Toxicities (DLT) in Cycle 1 of Part A | The maximum tolerated dose (MTD) is defined as the maximum dose of IPN60090 administered BID for 21 days, so that no more than 30% of participants experience a DLT. The MTD was determined using a Bayesian Optimal Interval design. The DLT assessment period was the first 21 days of treatment (one cycle). | DLT evaluable population included all participants from the safety population who were evaluable for DLT (participants who completed at least one cycle of treatment and received ≥75% of the total planned dose of IPN60090 over the DLT assessment period). | Posted | Count of Participants | Participants | No | Up to Cycle 1 Day 21 of Part A |
|
|
|
| Primary | Recommended Dose of IPN60090 in Part A | The recommended dose was determined by the safety review committee following an ad-hoc review of the safety and tolerability data during Part A of the study. | DLT evaluable population included all participants from the safety population who were evaluable for DLT (participants who completed at least one cycle of treatment and received ≥75% of the total planned dose of IPN60090 over the DLT assessment period). | Posted | Number | mg | Up to Cycle 1 Day 21 of Part A |
|
|
|
| Secondary | Best Overall Response (BOR) in Part A | The BOR is defined as the best response designation [in the order of complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD)] for each participant that is recorded between the date of the first dose of the study drug and the date of documented disease progression per RECIST 1.1 or the date of subsequent anticancer therapy whichever occurs first. Per RECIST v1.1, CR is disappearance of all target lesions; PR is >=30% decrease in the sum of the longest diameter of target lesions; and overall response = CR + PR. | Efficacy population included all participants who received at least one dose of IPN60090. | Posted | Count of Participants | Participants | No | RECIST assessments performed at baseline (within 28 days before start of study drug), every 6 weeks +/-1 week for first 24 weeks, then every 12 weeks +/-2 weeks thereafter. Up to data cut-off for study termination (maximum of 247 days). |
|
|
|
| Secondary | Objective Response Rate (ORR) in Part A | The ORR is defined as the percentage of participants in whom the BOR is equal to CR and PR for Part A. The BOR is defined as the best response designation (in the order of CR, PR, SD, PD) for each participant that is recorded between the date of the first dose of the study drug and the date of documented disease progression per RECIST 1.1 or the date of subsequent anticancer therapy whichever occurs first. Per RECIST v1.1, CR is disappearance of all target lesions; PR is >=30% decrease in the sum of the longest diameter of target lesions; and overall response = CR + PR. | Efficacy population included all participants who received at least one dose of IPN60090. | Posted | Number | 95% Confidence Interval | percentage of participants | RECIST assessments performed at baseline (within 28 days before start of study drug), every 6 weeks +/-1 week for first 24 weeks, then every 12 weeks +/-2 weeks thereafter. Up to data cut-off for study termination (maximum of 247 days). |
|
|
|
| Secondary | Disease Control Rate (DCR) in Part A | The DCR is defined as the percentage of participants in whom the BOR is equal to CR, PR or SD for Part A. The BOR is defined as the best response designation (in the order of CR, PR, SD, PD) for each participant that is recorded between the date of the first dose of the study drug and the date of documented disease progression per RECIST 1.1 or the date of subsequent anticancer therapy whichever occurs first. Per RECIST v1.1, CR is disappearance of all target lesions; PR is >=30% decrease in the sum of the longest diameter of target lesions; and overall response = CR + PR. | Efficacy population included all participants who received at least one dose of IPN60090. | Posted | Number | 95% Confidence Interval | percentage of participants | RECIST assessments performed at baseline (within 28 days before start of study drug), every 6 weeks +/-1 week for first 24 weeks, then every 12 weeks +/-2 weeks thereafter. Up to data cut-off for study termination (maximum of 247 days). |
|
|
|
| Secondary | Mean Progression Free Survival (PFS) in Part A | The PFS is defined as the time from first dose of study drug to the first documented objective disease progression (for RECIST 1.1), clinical disease progression collected at end of treatment, or death due to any cause, whichever occurred first. Per RECIST 1.1, progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. | Efficacy population included all participants who received at least one dose of IPN60090. | Posted | Mean | Standard Deviation | months | RECIST assessments performed at baseline (within 28 days before start of study drug), every 6 weeks +/-1 week for first 24 weeks, then every 12 weeks +/-2 weeks thereafter. Up to data cut-off for study termination (maximum of 247 days). |
|
|
|
| Secondary | Mean Overall Survival (OS) in Part A | The OS is defined as the time from first dose of study drug to death due to any cause. Participants who were lost to follow-up or who were still alive at the time of analysis is censored at the last day the participant was known to be alive or data cut-off date, whichever occurred first. | Efficacy population included all participants who received at least one dose of IPN60090. | Posted | Mean | Standard Deviation | months | RECIST assessments performed at baseline (within 28 days before start of study drug), every 6 weeks +/-1 week for first 24 weeks, then every 12 weeks +/-2 weeks thereafter. Up to data cut-off for study termination (maximum of 247 days). |
|
|
|
| Secondary | Mean Best Percent Change From Baseline in the Sum of Diameters of the Target Lesions at Minimum Post-Baseline in Part A | All measurable lesions up to a maximum of two lesions per organ and five lesions in total, representative of all involved organs, identified as target lesions and measured at baseline. Baseline is defined as the last measurement prior to the first dose of study drug. | Efficacy population included all participants who received at least one dose of IPN60090. Only participants with valid baseline and at least one post-baseline value of the sum of diameters are included. | Posted | Mean | Standard Deviation | percent change | Baseline (within 28 days before start of study drug) and post-baseline, up to data cut-off for study termination (maximum of 247 days). |
|
|
|
| Secondary | Maximum Observed Concentration (Cmax) of IPN60090 in Part A | Blood samples were collected to determine Cmax of IPN60090. The pharmacokinetics (PK) of IPN60090 plasma concentrations were performed using noncompartmental analysis. | The PK population for noncompartmental analysis included all participants who had no major protocol deviation affecting the PK variables and who had a sufficient number of IPN60090 plasma concentrations to estimate the main PK parameters. Summarized PK results are presented for IPN60090 120 mg, IPN60090 180 mg and IPN60090 240 mg reporting groups only. | Posted | Mean | Standard Deviation | nanogram per milliliter (ng/mL) | Pre-dose and 0.5, 1, 2, 4, 8 and 12 hours post-dose on Cycle 1 Day 1 and Cycle 1 Day 14 in Part A |
|
|
|
| Secondary | Time to Reach Maximum Observed Concentration (Tmax) of IPN60090 in Part A | Blood samples were collected to determine Tmax of IPN60090. The PK of IPN60090 plasma concentrations were performed using noncompartmental analysis. | The PK population for noncompartmental analysis included all participants who had no major protocol deviation affecting the PK variables and who had a sufficient number of IPN60090 plasma concentrations to estimate the main PK parameters. Summarized PK results are presented for IPN60090 120 mg, IPN60090 180 mg and IPN60090 240 mg reporting groups only. | Posted | Median | Full Range | hours | Pre-dose and 0.5, 1, 2, 4, 8 and 12 hours post-dose on Cycle 1 Day 1 and Cycle 1 Day 14 in Part A |
|
|
|
| Secondary | Trough Plasma Concentration (Ctrough) of IPN60090 in Part A | Blood samples were collected to determine Ctrough of IPN60090. The PK of IPN60090 plasma concentrations were performed using noncompartmental analysis. | The PK population for noncompartmental analysis included all participants who had no major protocol deviation affecting the PK variables and who had a sufficient number of IPN60090 plasma concentrations to estimate the main PK parameters. Summarized PK results are presented for IPN60090 120 mg, IPN60090 180 mg and IPN60090 240 mg reporting groups only. | Posted | Mean | Standard Deviation | ng/mL | Pre-dose and 0.5, 1, 2, 4, 8 and 12 hours post-dose on Cycle 1 Day 14 in Part A |
|
|
|
| Secondary | Area Under the Concentration Versus Time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) of IPN60090 in Part A | Blood samples were collected to determine AUC0-last of IPN60090. The PK of IPN60090 plasma concentrations were performed using noncompartmental analysis. | The PK population for noncompartmental analysis included all participants who had no major protocol deviation affecting the PK variables and who had a sufficient number of IPN60090 plasma concentrations to estimate the main PK parameters. Summarized PK results are presented for IPN60090 120 mg, IPN60090 180 mg and IPN60090 240 mg reporting groups only. | Posted | Mean | Standard Deviation | hour*ng/mL | Pre-dose and 0.5, 1, 2, 4, 8 and 12 hours post-dose on Cycle 1 Day 1 and Cycle 1 Day 14 in Part A |
|
|
|
| Secondary | Apparent Elimination Half-Life (T1/2) of IPN60090 in Part A | Blood samples were collected to determine T1/2 of IPN60090. The PK of IPN60090 plasma concentrations were performed using noncompartmental analysis. | The PK population for noncompartmental analysis included all participants who had no major protocol deviation affecting the PK variables and who had a sufficient number of IPN60090 plasma concentrations to estimate the main PK parameters. Summarized PK results are presented for IPN60090 120 mg, IPN60090 180 mg and IPN60090 240 mg reporting groups only. | Posted | Median | Full Range | hours | Pre-dose and 0.5, 1, 2, 4, 8 and 12 hours post-dose on Cycle 1 Day 1 in Part A |
|
|
|
| Secondary | Apparent Total Body Clearance (CL/F) of IPN60090 in Part A | Blood samples were collected to determine CL/F of IPN60090. The PK of IPN60090 plasma concentrations were performed using noncompartmental analysis. | The PK population for noncompartmental analysis included all participants who had no major protocol deviation affecting the PK variables and who had a sufficient number of IPN60090 plasma concentrations to estimate the main PK parameters. Summarized PK results are presented for IPN60090 120 mg, IPN60090 180 mg and IPN60090 240 mg reporting groups only. | Posted | Mean | Standard Deviation | liter per hour | Pre-dose and 0.5, 1, 2, 4, 8 and 12 hours post-dose on Cycle 1 Day 1 in Part A |
|
|
|
| Secondary | Apparent Volume of Distribution (Vz/F) of IPN60090 in Part A | Blood samples were collected to determine Vz/F of IPN60090. The PK of IPN60090 plasma concentrations were performed using noncompartmental analysis. | The PK population for noncompartmental analysis included all participants who had no major protocol deviation affecting the PK variables and who had a sufficient number of IPN60090 plasma concentrations to estimate the main PK parameters. Summarized PK results are presented for IPN60090 120 mg, IPN60090 180 mg and IPN60090 240 mg reporting groups only. | Posted | Mean | Standard Deviation | liter | Pre-dose and 0.5, 1, 2, 4, 8 and 12 hours post-dose on Cycle 1 Day 1 in Part A |
|
|
|
| Secondary | Target Engagement in Part A | The target engagement is glutamate:glutamine (Glu:Gln) ratio in peripheral blood mononuclear cells. Glu:Gln ratio inhibition is calculated as (1 - post-baseline Glu:Gln ratio/Cycle 1 Day 1 predose Glu:Gln ratio) x 100%. | Efficacy population included all participants who received at least one dose of IPN60090. | Posted | Mean | Standard Deviation | ratio | At 2 and 12 hours postdose on Cycle 1 Day 1; predose, 2 and 12 hours postdose on Cycle 1 Day 14; and predose, 2 and 2-4 hours postdose on Cycle 1 Day 15 in Part A |
|
|
|
| 0 |
| 1 |
| 1 |
| 1 |
| 1 |
| 1 |
| EG001 | IPN60090 40 mg | Participants received IPN60090 40 mg capsules orally BID up to Cycle 2 in Part A of the study. | 0 | 1 | 0 | 1 | 1 | 1 |
| EG002 | IPN60090 80 mg | Participants received IPN60090 80 mg capsules orally BID up to Cycle 5 in Part A of the study. | 0 | 1 | 1 | 1 | 1 | 1 |
| EG003 | IPN60090 120 mg | Participants received IPN60090 120 mg capsules orally BID up to Cycle 9 in Part A of the study. | 0 | 4 | 2 | 4 | 4 | 4 |
| EG004 | IPN60090 180 mg | Participants received IPN60090 180 mg capsules orally BID up to Cycle 9 in Part A of the study. | 0 | 11 | 4 | 11 | 11 | 11 |
| EG005 | IPN60090 240 mg | Participants received IPN60090 240 mg capsules orally BID up to Cycle 4 in Part A of the study. | 0 | 4 | 3 | 4 | 4 | 4 |
| Abdominal pain | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Haematochezia | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Upper gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Aeromonas infection | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
|
| COVID-19 | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
|
| Clostridium difficile infection | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
|
| Cryptosporidiosis infection | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
|
| Pyelonephritis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
|
| Brain oedema | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
|
| Cerebrovascular accident | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
|
| Seizure | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
|
| Biliary obstruction | Hepatobiliary disorders | MedDRA 23.1 | Systematic Assessment |
|
| Cholecystitis | Hepatobiliary disorders | MedDRA 23.1 | Systematic Assessment |
|
| Pathological fracture | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
|
| Atrial fibrillation | Cardiac disorders | MedDRA 23.1 | Systematic Assessment |
|
| Vertigo | Ear and labyrinth disorders | MedDRA 23.1 | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | MedDRA 23.1 | Systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
|
| Cancer pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.1 | Systematic Assessment |
|
| Acute kidney injury | Renal and urinary disorders | MedDRA 23.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Abdominal pain lower | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Gastric haemorrhage | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Oesophageal stenosis | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Oesophagitis | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Rectal haemorrhage | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Hypertriglyceridaemia | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
|
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
|
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
|
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
|
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
|
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
|
| Increased appetite | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
|
| Photopsia | Eye disorders | MedDRA 23.1 | Systematic Assessment |
|
| Photophobia | Eye disorders | MedDRA 23.1 | Systematic Assessment |
|
| Vision blurred | Eye disorders | MedDRA 23.1 | Systematic Assessment |
|
| Visual impairment | Eye disorders | MedDRA 23.1 | Systematic Assessment |
|
| Vitreous floaters | Eye disorders | MedDRA 23.1 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
|
| Migraine with aura | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
|
| Facial paralysis | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
|
| Hypoaesthesia | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
|
| Posterior reversible encephalopathy syndrome | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
|
| Tremor | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 23.1 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 23.1 | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA 23.1 | Systematic Assessment |
|
| Oedema | General disorders | MedDRA 23.1 | Systematic Assessment |
|
| Peripheral swelling | General disorders | MedDRA 23.1 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
|
| Cellulitis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
|
| Cystitis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
|
| Oral candidiasis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA 23.1 | Systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA 23.1 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA 23.1 | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | MedDRA 23.1 | Systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA 23.1 | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA 23.1 | Systematic Assessment |
|
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA 23.1 | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 23.1 | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
|
| Rash pruritic | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
|
| Rash papular | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 23.1 | Systematic Assessment |
|
| Deep vein thrombosis | Vascular disorders | MedDRA 23.1 | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA 23.1 | Systematic Assessment |
|
| Cancer pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.1 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA 23.1 | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA 23.1 | Systematic Assessment |
|
| Hallucination | Psychiatric disorders | MedDRA 23.1 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
|
| Atrial fibrillation | Cardiac disorders | MedDRA 23.1 | Systematic Assessment |
|
| Sinus tachycardia | Cardiac disorders | MedDRA 23.1 | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA 23.1 | Systematic Assessment |
|
| Pollakiuria | Renal and urinary disorders | MedDRA 23.1 | Systematic Assessment |
|
Not provided
Not provided
| D006844 |
| Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| PR |
|
| SD |
|
| PD |
|
| Not evaluable |
|
| Cycle 1 Day 14 |
|
|
| Cycle 1 Day 14 |
|
|
| Cycle 1 Day 14 |
|
|
|
| Cycle 1 Day 1: 12 hours postdose |
|
|
| Cycle 1 Day 14: predose |
|
|
| Cycle 1 Day 14: 2 hours postdose |
|
|
| Cycle 1 Day 14: 12 hours postdose |
|
|
| Cycle 1 Day 15: predose |
|
|
| Cycle 1 Day 15: 2 hours postdose |
|
|
| Cycle 1 Day 15: 2-4 hours postdose |
|
|