NCT02319369 is a Phase 1 clinical trial of Milademetan in Acute Myelogenous Leukemia, sponsored by Daiichi Sankyo.

Who is sponsoring NCT02319369?

NCT02319369 is sponsored by Daiichi Sankyo.

What drugs are being tested in NCT02319369?

Interventions in NCT02319369: Milademetan, AZA, Milademetan.

What condition does NCT02319369 study?

NCT02319369 studies Acute Myelogenous Leukemia, Myelodysplastic Syndrome.

Is NCT02319369 still recruiting?

NCT02319369 is currently terminated. Last updated 11 October 2021.

Are results published for NCT02319369?

Yes — primary outcome results have been posted to ClinicalTrials.gov. See the outcomes section above for details.

Last reviewed 2021-10-11 · How we verify

NCT02319369

Name: Drug Landscape Pharmaceutical Database
Creator: Drug Landscape
Published: 2026-01-01
License: https://creativecommons.org/licenses/by/4.0/

Safety, Tolerability and Pharmacokinetics of Milademetan Alone and With 5-Azacitidine (AZA) in Acute Myelogenous Leukemia (AML) or High-Risk Myelodysplastic Syndrome (MDS)

Terminated Phase 1 Results posted Last updated 11 October 2021

What this trial tests

Phase 1 trial testing Milademetan in Acute Myelogenous Leukemia in 74 participants. Terminated before completion.

Timeline

25 November 2014

Primary endpoint
21 August 2020

21 August 2020

Quick facts

Lead sponsor	Daiichi Sankyo
Phase	Phase 1
Status	Terminated
Study type	INTERVENTIONAL
Allocation	non randomized
Design	sequential
Masking	none
Primary purpose	treatment
Enrollment	74
Start date	25 November 2014
Primary completion	21 August 2020
Estimated completion	21 August 2020
Sites	5 locations across United States

Drugs / interventions tested

Milademetan — full drug profile →
AZA — full drug profile →
Milademetan — full drug profile →

Conditions studied

Acute Myelogenous Leukemia — all drugs for Acute Myelogenous Leukemia →
Myelodysplastic Syndrome — all drugs for Myelodysplastic Syndrome →

Sponsor

Daiichi Sankyo — full company profile →

Who can join

18 and older, any sex, with Acute Myelogenous Leukemia or Myelodysplastic Syndrome. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) Primary · From the date the participant signed the informed consent form up to 5 years of first participant enrolled

A DLT was defined as any treatment-emergent adverse event not attributable to disease or disease-related processes occurring during the observation period (Cycle 1) in each dose-level cohort and is Grade (Gr) 3 or higher according to NCI CTCAE Version 5.0 (Version 4.03 before 01 Apr 2018), with these exceptions: for elevations in hepatic function enzymes, a DLT is defined as: Gr ≥3 aspartate aminotransferase (AST)/alanine aminotransferase (ALT) levels lasting \>3 days; AST/ALT \>5 × ULN if accompanied by ≥Gr 2 elevation in bilirubin. Potential DLTs include: Participants who are unable to compl

Participants with TEAEs classified as DLTs

Group	Value	95% CI
Cohort 1: Milademetan 60 mg	1
Cohort 4: Milademetan 160 mg	2
Cohort 5: Milademetan 210 mg	3
Cohort 9d: Milademetan 220 mg	2
Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2	2

Nausea

Group	Value	95% CI
Cohort 1: Milademetan 60 mg	0
Cohort 4: Milademetan 160 mg	0
Cohort 5: Milademetan 210 mg	1
Cohort 9d: Milademetan 220 mg	2
Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2	0

Fatigue

Group	Value	95% CI
Cohort 1: Milademetan 60 mg	0
Cohort 4: Milademetan 160 mg	0
Cohort 5: Milademetan 210 mg	1
Cohort 9d: Milademetan 220 mg	0
Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2	2

Cellulitis

Group	Value	95% CI
Cohort 1: Milademetan 60 mg	0
Cohort 4: Milademetan 160 mg	0
Cohort 5: Milademetan 210 mg	1
Cohort 9d: Milademetan 220 mg	0
Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2	0

Diarrhoea

Group	Value	95% CI
Cohort 1: Milademetan 60 mg	0
Cohort 4: Milademetan 160 mg	1
Cohort 5: Milademetan 210 mg	0
Cohort 9d: Milademetan 220 mg	0
Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2	0

Hypokalaemia

Group	Value	95% CI
Cohort 1: Milademetan 60 mg	0
Cohort 4: Milademetan 160 mg	1
Cohort 5: Milademetan 210 mg	0
Cohort 9d: Milademetan 220 mg	0
Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2	0

Renal failure

Group	Value	95% CI
Cohort 1: Milademetan 60 mg	0
Cohort 4: Milademetan 160 mg	0
Cohort 5: Milademetan 210 mg	1
Cohort 9d: Milademetan 220 mg	0
Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2	0

Vomiting

Group	Value	95% CI
Cohort 1: Milademetan 60 mg	1
Cohort 4: Milademetan 160 mg	0
Cohort 5: Milademetan 210 mg	0
Cohort 9d: Milademetan 220 mg	0
Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2	0

Number of Participants (≥10%) With Treatment-emergent Adverse Events (TEAEs) Following Administration of Milademetan Alone and In Combination With 5-Azacitidine (AZA) Primary · From the date the participant signed the informed consent form up to 30 days after the last dose in the last participant, up to approximately 6 years of first participant enrolled

A treatment-emergent adverse event (TEAE) is defined as an adverse event that emerges during the treatment period (up to 30 days after last dose), having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pre-treatment state, when the adverse event is continuous.

Any TEAEs

Group	Value	95% CI
Cohort 1: Milademetan 60 mg	7
Cohort 2: Milademetan 90 mg	6
Cohort 3: Milademetan 120 mg	11
Cohort 4: Milademetan 160 mg	8
Cohort 5: Milademetan 210 mg	5
Cohort 6b: Milademetan 160 mg	7
Cohort 7c: Milademetan 160 mg	3
Cohort 8d: Milademetan 160 mg	6
Cohort 9d: Milademetan 220 mg	4
Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2	9
Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2	3
Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2	4

Nausea

Group	Value	95% CI
Cohort 1: Milademetan 60 mg	5
Cohort 2: Milademetan 90 mg	4
Cohort 3: Milademetan 120 mg	8
Cohort 4: Milademetan 160 mg	6
Cohort 5: Milademetan 210 mg	4
Cohort 6b: Milademetan 160 mg	3
Cohort 7c: Milademetan 160 mg	2
Cohort 8d: Milademetan 160 mg	4
Cohort 9d: Milademetan 220 mg	3
Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2	5
Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2	2
Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2	2

Diarrhoea

Group	Value	95% CI
Cohort 1: Milademetan 60 mg	2
Cohort 2: Milademetan 90 mg	2
Cohort 3: Milademetan 120 mg	8
Cohort 4: Milademetan 160 mg	5
Cohort 5: Milademetan 210 mg	3
Cohort 6b: Milademetan 160 mg	4
Cohort 7c: Milademetan 160 mg	2
Cohort 8d: Milademetan 160 mg	3
Cohort 9d: Milademetan 220 mg	3
Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2	1
Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2	2
Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2	1

Vomiting

Group	Value	95% CI
Cohort 1: Milademetan 60 mg	2
Cohort 2: Milademetan 90 mg	1
Cohort 3: Milademetan 120 mg	4
Cohort 4: Milademetan 160 mg	4
Cohort 5: Milademetan 210 mg	3
Cohort 6b: Milademetan 160 mg	2
Cohort 7c: Milademetan 160 mg	2
Cohort 8d: Milademetan 160 mg	3
Cohort 9d: Milademetan 220 mg	3
Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2	3
Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2	2
Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2	0

Fatigue

Group	Value	95% CI
Cohort 1: Milademetan 60 mg	2
Cohort 2: Milademetan 90 mg	1
Cohort 3: Milademetan 120 mg	5
Cohort 4: Milademetan 160 mg	5
Cohort 5: Milademetan 210 mg	3
Cohort 6b: Milademetan 160 mg	2
Cohort 7c: Milademetan 160 mg	0
Cohort 8d: Milademetan 160 mg	1
Cohort 9d: Milademetan 220 mg	1
Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2	3
Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2	2
Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2	2

Thrombocytopenia

Group	Value	95% CI
Cohort 1: Milademetan 60 mg	2
Cohort 2: Milademetan 90 mg	1
Cohort 3: Milademetan 120 mg	4
Cohort 4: Milademetan 160 mg	5
Cohort 5: Milademetan 210 mg	1
Cohort 6b: Milademetan 160 mg	1
Cohort 7c: Milademetan 160 mg	0
Cohort 8d: Milademetan 160 mg	0
Cohort 9d: Milademetan 220 mg	1
Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2	0
Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2	0
Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2	3

Oedema peripheral

Group	Value	95% CI
Cohort 1: Milademetan 60 mg	1
Cohort 2: Milademetan 90 mg	0
Cohort 3: Milademetan 120 mg	4
Cohort 4: Milademetan 160 mg	2
Cohort 5: Milademetan 210 mg	1
Cohort 6b: Milademetan 160 mg	3
Cohort 7c: Milademetan 160 mg	1
Cohort 8d: Milademetan 160 mg	1
Cohort 9d: Milademetan 220 mg	1
Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2	1
Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2	1
Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2	1

Anaemia

Group	Value	95% CI
Cohort 1: Milademetan 60 mg	2
Cohort 2: Milademetan 90 mg	3
Cohort 3: Milademetan 120 mg	3
Cohort 4: Milademetan 160 mg	3
Cohort 5: Milademetan 210 mg	1
Cohort 6b: Milademetan 160 mg	1
Cohort 7c: Milademetan 160 mg	0
Cohort 8d: Milademetan 160 mg	0
Cohort 9d: Milademetan 220 mg	0
Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2	0
Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2	0
Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2	0

Maximum Plasma Concentration (Cmax) Following Administration of Milademetan Alone Secondary · Predose, 1 hour (hr), 2 hr, 3 hr, 6 hr, 8 hr, 10 hr of Cycle 1, Day 1 (Cohorts 1-9d) and Cycle 1, Day 15 (Cohorts 1-5 and 7c) (each cycle is 28 days)

Pharmacokinetic parameter maximum plasma concentration (Cmax) of milademetan was assessed at select time points and the geometric means (coefficient of variation %) are presented.

Cycle 1, Day 1

Group	Value	95% CI
Cohort 1: Milademetan 60 mg	386.0	± 42.2
Cohort 2: Milademetan 90 mg	342.5	± 23.4
Cohort 3: Milademetan 120 mg	505.9	± 56.8
Cohort 4: Milademetan 160 mg	622.3	± 94.5
Cohort 5: Milademetan 210 mg	747.9	± 48.1
Cohort 6b: Milademetan 160 mg	440.0	± 74.7
Cohort 7c: Milademetan 160 mg	758.1	± 44.8
Cohort 8d: Milademetan 160 mg	657.0	± 27.2
Cohort 9d: Milademetan 220 mg	1607.4	± 34.4

Cycle 1, Day 15

Group	Value	95% CI
Cohort 1: Milademetan 60 mg	498.5	± 40.3
Cohort 2: Milademetan 90 mg	562.6	± 58.6
Cohort 3: Milademetan 120 mg	614.3	± 55.3
Cohort 4: Milademetan 160 mg	753.8	± 79.8
Cohort 5: Milademetan 210 mg	1329.2	± 21.9
Cohort 6b: Milademetan 160 mg	NA	± NA
Cohort 7c: Milademetan 160 mg	669.2	± 46.0
Cohort 8d: Milademetan 160 mg	NA	± NA
Cohort 9d: Milademetan 220 mg	NA	± NA

Maximum Plasma Concentration (Cmax) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) Secondary · Predose, 0.5 hour (hr), 1 hr, 2 hr, 3 hr, 6 hr of Cycle 1, Day 1 (AZA); Predose, 0.5 hr, 1 hr, 2 hr, 3 hr, 4 hr, 6-10 hr of Day 5, Day 7 (predose) (Cohorts 10e and 12e), Day 8 (Cohorts 11f and 13f), and Day 14 (Cohorts 10e-13f) (each cycle is 28 days)

Pharmacokinetic parameter maximum plasma concentration (Cmax) was assessed at select time points and the geometric means (coefficient of variation %) are presented.

Cycle 1, Day 1

Group	Value	95% CI
Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2	527.0	± 61.9
Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2	NA	± NA
Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2	707.0	± 37.7
Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2	NA	± NA

Cycle 1, Day 5

Group	Value	95% CI
Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2	704.8	± 57.6
Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2	NA	± NA
Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2	1019.6	± 72.2
Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2	NA	± NA

Cycle 1, Day 7

Group	Value	95% CI
Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2	702.5	± 46.4
Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2	NA	± NA
Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2	769.8	± 46.7
Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2	NA	± NA

Cycle 1, Day 8

Group	Value	95% CI
Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2	NA	± NA
Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2	327.5	± 51.2
Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2	NA	± NA
Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2	266.0	± NA

Cycle 1, Day 14

Group	Value	95% CI
Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2	1488.6	± 55.2
Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2	1057.9	± 20.4
Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2	1448.2	± 57.2
Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2	1190.0	± NA

Time to Maximum Concentration (Tmax) Following Administration of Milademetan Alone Secondary · Predose, 1 hour (hr), 2 hr, 3 hr, 6 hr, 8 hr, 10 hr of Cycle 1, Day 1 (Cohorts 1-9d) and Cycle 1, Day 15 (Cohorts 1-5 and 7c) (each cycle is 28 days)

Pharmacokinetic parameter time to maximum concentration (Tmax) of milademetan was assessed at select time points.

Cycle 1, Day 1

Group	Value	95% CI
Cohort 1: Milademetan 60 mg	3.00	2.00 – 6.25
Cohort 2: Milademetan 90 mg	4.39	1.98 – 6.08
Cohort 3: Milademetan 120 mg	3.00	2.00 – 6.25
Cohort 4: Milademetan 160 mg	4.50	1.90 – 6.07
Cohort 5: Milademetan 210 mg	3.00	3.00 – 8.07
Cohort 6b: Milademetan 160 mg	3.00	2.05 – 10.00
Cohort 7c: Milademetan 160 mg	3.08	2.00 – 6.00
Cohort 8d: Milademetan 160 mg	4.50	3.00 – 6.00
Cohort 9d: Milademetan 220 mg	4.56	3.00 – 6.17

Cycle 1, Day 15

Group	Value	95% CI
Cohort 1: Milademetan 60 mg	3.00	2.00 – 3.28
Cohort 2: Milademetan 90 mg	2.99	2.00 – 6.00
Cohort 3: Milademetan 120 mg	3.00	2.00 – 6.00
Cohort 4: Milademetan 160 mg	2.96	1.08 – 6.00
Cohort 5: Milademetan 210 mg	4.50	2.92 – 6.00
Cohort 6b: Milademetan 160 mg	NA	NA – NA
Cohort 7c: Milademetan 160 mg	3.04	3.00 – 3.08
Cohort 8d: Milademetan 160 mg	NA	NA – NA
Cohort 9d: Milademetan 220 mg	NA	NA – NA

Time to Maximum Concentration (Tmax) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) Secondary · Predose, 0.5 hour (hr), 1 hr, 2 hr, 3 hr, 6 hr of Cycle 1, Day 1 (AZA); Predose, 0.5 hr, 1 hr, 2 hr, 3 hr, 4 hr, 6-10 hr of Day 5, Day 7 (predose) (Cohorts 10e and 12e), Day 8 (Cohorts 11f and 13f), and Day 14 (Cohorts 10e-13f) (each cycle is 28 days)

Pharmacokinetic parameter time to maximum concentration (Tmax) was assessed at select time points.

Cycle 1, Day 1

Group	Value	95% CI
Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2	0.77	0.48 – 2.00
Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2	NA	NA – NA
Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2	0.51	0.48 – 0.58
Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2	NA	NA – NA

Cycle 1, Day 5

Group	Value	95% CI
Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2	3.02	2.05 – 6.07
Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2	NA	NA – NA
Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2	4.41	2.10 – 8.00
Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2	NA	NA – NA

Cycle 1, Day 7

Group	Value	95% CI
Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2	0.56	0.48 – 0.98
Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2	NA	NA – NA
Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2	0.58	0.50 – 1.00
Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2	NA	NA – NA

Cycle 1, Day 8

Group	Value	95% CI
Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2	NA	NA – NA
Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2	6.33	6.07 – 8.97
Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2	NA	NA – NA
Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2	3.08	3.08 – 3.08

Cycle 1, Day 14

Group	Value	95% CI
Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2	3.00	2.05 – 10.00
Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2	6.05	3.17 – 8.00
Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2	5.54	3.08 – 8.00
Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2	6.15	6.15 – 6.15

Trough Plasma Concentration (Ctrough) Following Administration of Milademetan Alone Secondary · Predose, 1 hour (hr), 2 hr, 3 hr, 6 hr, 8 hr, 10 hr of Cycle 1, Day 15 (Cohorts 1-5 and 7c) (each cycle is 28 days)

Pharmacokinetic parameter plasma concentration before next dose (Ctrough) of milademetan was assessed at Cycle 1, Day 15 and the geometric means (coefficient of variation %) are presented.

Group	Value	95% CI
Cohort 1: Milademetan 60 mg	197.13	± 23.2
Cohort 2: Milademetan 90 mg	229.28	± 82.0
Cohort 3: Milademetan 120 mg	292.60	± 59.7
Cohort 4: Milademetan 160 mg	184.60	± 279.1
Cohort 5: Milademetan 210 mg	507.07	± 24.0
Cohort 7c: Milademetan 160 mg	NA	± NA

Area Under the Plasma Concentration Curve up to 24 Hours (AUC0-24) Following Administration of Milademetan Alone Secondary · Predose, 1 hour (hr), 2 hr, 3 hr, 6 hr, 8 hr, 10 hr of Cycle 1, Day 1 (Cohorts 1-9d) and Cycle 1, Day 15 (Cohorts 1-5 and 7c) (each cycle is 28 days)

Pharmacokinetic parameter area under the plasma concentration curve up to 24 hours (AUC0-24) of milademetan was assessed at select time points and the geometric means (coefficient of variation %) are presented.

Cycle 1, Day 1

Group	Value	95% CI
Cohort 1: Milademetan 60 mg	4646.7	± 47.7
Cohort 2: Milademetan 90 mg	4478.1	± 31.2
Cohort 3: Milademetan 120 mg	6585.4	± 54.8
Cohort 4: Milademetan 160 mg	8315.1	± 101.2
Cohort 5: Milademetan 210 mg	9794.0	± 39.4
Cohort 6b: Milademetan 160 mg	7222.5	± 43.1
Cohort 7c: Milademetan 160 mg	10165.6	± 64.6
Cohort 8d: Milademetan 160 mg	8973.9	± 28.1
Cohort 9d: Milademetan 220 mg	20893.9	± 23.2

Cycle 1, Day 15

Group	Value	95% CI
Cohort 1: Milademetan 60 mg	7244.6	± 28.9
Cohort 2: Milademetan 90 mg	8392.9	± 56.5
Cohort 3: Milademetan 120 mg	9854.9	± 54.6
Cohort 4: Milademetan 160 mg	10710.8	± 54.2
Cohort 5: Milademetan 210 mg	20330.2	± 15.9
Cohort 6b: Milademetan 160 mg	NA	± NA
Cohort 7c: Milademetan 160 mg	7714.3	± 30.5
Cohort 8d: Milademetan 160 mg	NA	± NA
Cohort 9d: Milademetan 220 mg	NA	± NA

Area Under the Plasma Concentration Curve up to 24 Hours (AUC0-24) Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) Secondary · Predose, 0.5 hr, 1 hr, 2 hr, 3 hr, 4 hr, 6-10 hr of Cycle 1, Day 5 (Cohorts 10e and 12e) and Predose of Cycle 1, Day 14 (Cohorts 10e, 11f, and 12e) (each cycle is 28 days)

Pharmacokinetic parameter area under the plasma concentration curve up to 24 hours (AUC0-24) was assessed at select time points and the geometric means (coefficient of variation %) are presented.

Cycle 1, Day 5

Group	Value	95% CI
Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2	8238.7	± 43.0
Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2	NA	± NA
Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2	21299.3	± 16.3

Cycle 1, Day 14

Group	Value	95% CI
Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2	22563.8	± 52.9
Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2	15755.5	± 29.4
Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2	19967.5	± 18.5

Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan Alone Secondary · Day 1 (6 hours postdose) up to Day 21-22 (predose), up to approximately 6 years of first participant enrolled

Pharmacodynamic biomarker serum macrophage inhibitory cytokine-1 (MIC-1) concentrations of milademetan were assessed for Cohorts 1 though 9d. Fold change is the ratio of post-baseline MIC-1 values with respect to the baseline values and is the measure of change of MIC-1 from baseline.

Day 1 (6 hours postdose)

Group	Value	95% CI
Cohort 1: Milademetan 60 mg	3.14	± 1.23
Cohort 2: Milademetan 90 mg	2.78	± 0.95
Cohort 3: Milademetan 120 mg	3.36	± 1.38
Cohort 4: Milademetan 160 mg	3.00	± 0.88
Cohort 5: Milademetan 210 mg	4.25	± 1.41
Cohort 6b: Milademetan 160 mg	2.64	± 0.91
Cohort 7c: Milademetan 160 mg	3.36	± 1.49
Cohort 8d: Milademetan 160 mg	2.64	± 0.87
Cohort 9d: Milademetan 220 mg	4.94	± 2.22

Day 2 (predose)

Group	Value	95% CI
Cohort 1: Milademetan 60 mg	2.53	± 0.83
Cohort 2: Milademetan 90 mg	3.31	± 1.25
Cohort 3: Milademetan 120 mg	3.97	± 2.71
Cohort 4: Milademetan 160 mg	3.44	± 1.63
Cohort 5: Milademetan 210 mg	5.06	± 2.62
Cohort 6b: Milademetan 160 mg	2.57	± 0.81
Cohort 7c: Milademetan 160 mg	3.84	± 1.74
Cohort 8d: Milademetan 160 mg	3.68	± 2.13
Cohort 9d: Milademetan 220 mg	8.09	± 3.27

Day 8 (predose)

Group	Value	95% CI
Cohort 1: Milademetan 60 mg	4.13	± 2.46
Cohort 2: Milademetan 90 mg	6.35	± 4.61
Cohort 3: Milademetan 120 mg	7.41	± 7.17
Cohort 4: Milademetan 160 mg	5.13	± 2.64
Cohort 5: Milademetan 210 mg	9.70	± 7.96
Cohort 6b: Milademetan 160 mg	4.93	± 3.32
Cohort 7c: Milademetan 160 mg	1.44	± 0.36
Cohort 8d: Milademetan 160 mg	5.63	± 3.99
Cohort 9d: Milademetan 220 mg	13.68	± 10.72

Day 15 (predose)

Group	Value	95% CI
Cohort 1: Milademetan 60 mg	2.88	± 0.64
Cohort 2: Milademetan 90 mg	5.64	± 4.94
Cohort 3: Milademetan 120 mg	6.04	± 3.49
Cohort 4: Milademetan 160 mg	5.54	± 3.49
Cohort 5: Milademetan 210 mg	9.28	± 7.26
Cohort 6b: Milademetan 160 mg	1.33	± 0.98
Cohort 7c: Milademetan 160 mg	1.13	± 0.41
Cohort 8d: Milademetan 160 mg	5.02	± 2.20
Cohort 9d: Milademetan 220 mg	6.61	± 4.64

Day 21-22 (predose)

Group	Value	95% CI
Cohort 1: Milademetan 60 mg	3.49	± 1.88
Cohort 2: Milademetan 90 mg	4.61	± 2.66
Cohort 3: Milademetan 120 mg	4.57	± 3.53
Cohort 4: Milademetan 160 mg	6.57	± 4.22
Cohort 5: Milademetan 210 mg	5.88	± 2.75
Cohort 6b: Milademetan 160 mg	0.48	± NA
Cohort 7c: Milademetan 160 mg	1.24	± NA
Cohort 8d: Milademetan 160 mg	0.83	± 0.45
Cohort 9d: Milademetan 220 mg	1.18	± 0.60

Serum Macrophage Inhibitory Cytokine-1 (MIC-1) Fold Change From Baseline Following Administration of Milademetan In Combination With 5-Azacitidine (AZA) Secondary · Day 5 (predose) up to Day 22 (predose), up to approximately 6 years of first participant enrolled

Pharmacodynamic biomarker serum macrophage inhibitory cytokine-1 (MIC-1) concentrations were assessed for Cohorts 10e though 13f. Fold change is the ratio of post-baseline MIC-1 values with respect to the baseline values and is the measure of change of MIC-1 from baseline.

Day 5 (predose)

Group	Value	95% CI
Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2	1.65	± 0.72
Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2	1.39	± 0.36

Day 5 (6 hours postdose)

Group	Value	95% CI
Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2	3.12	± 2.38
Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2	6.07	± 2.99

Day 14 (predose)

Group	Value	95% CI
Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2	10.82	± 8.26
Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2	4.06	± 0.54
Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2	8.34	± 6.14

Day 22 (predose)

Group	Value	95% CI
Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2	2.05	± 2.34
Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2	1.38	± 0.29
Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2	1.81	± 1.20
Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2	1.83	± NA

Adverse events — posted to ClinicalTrials.gov

Time frame: Treatment-emergent adverse events (TEAEs) were collected from the date the participant signed the informed consent form up to 30 days after the last dose of study drug, up to approximately 6 years of first participant enrolled.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cohort 1: Milademetan 60 mg

Serious: 4/7 (57%)

Deaths: 1/7

Cohort 2: Milademetan 90 mg

Serious: 5/6 (83%)

Deaths: 0/6

Cohort 3: Milademetan 120 mg

Serious: 9/11 (82%)

Deaths: 1/11

Cohort 4: Milademetan 160 mg

Serious: 5/8 (63%)

Deaths: 1/8

Cohort 5: Milademetan 210 mg

Serious: 5/5 (100%)

Deaths: 1/5

Cohort 6b: Milademetan 160 mg

Serious: 4/7 (57%)

Deaths: 1/7

Cohort 7c: Milademetan 160 mg

Serious: 2/3 (67%)

Deaths: 1/3

Cohort 8d: Milademetan 160 mg

Serious: 3/6 (50%)

Deaths: 1/6

Cohort 9d: Milademetan 220 mg

Serious: 2/4 (50%)

Deaths: 2/4

Cohort 10e: Milademetan 160 mg + Azacitidine 75 mg/m^2

Serious: 9/9 (100%)

Deaths: 2/9

Cohort 11f: Milademetan 160 mg + Azacitidine 75 mg/m^2

Serious: 3/3 (100%)

Deaths: 2/3

Cohort 12e: Milademetan 200 mg + Azacitidine 75 mg/m^2

Serious: 4/4 (100%)

Deaths: 1/4

Cohort 13f: Milademetan 200 mg + Azacitidine 75 mg/m^2

Serious: 0/1 (0%)

Deaths: 0/1

Serious adverse events (53 terms)

Reaction	System	Cohort 1: Milademetan 60 mg	Cohort 2: Milademetan 90 mg	Cohort 3: Milademetan 120 mg	Cohort 4: Milademetan 160 mg	Cohort 5: Milademetan 210 mg	Cohort 6b: Milademetan 160…	Cohort 7c: Milademetan 160…	Cohort 8d: Milademetan 160…	Cohort 9d: Milademetan 220…	Cohort 10e: Milademetan 16…	Cohort 11f: Milademetan 16…	Cohort 12e: Milademetan 20…	Cohort 13f: Milademetan 20…
Lung infection	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—	—
Pneumonia	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—	—
Sepsis	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—	—
Febrile neutropenia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—
Death	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—
Bacteraemia	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—	—
Cellulitis	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—	—
Pneumonia fungal	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—	—
Arthritis bacterial	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—	—
Arthritis infective	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—	—
Clostridium difficile colitis	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—	—
Device related sepsis	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—	—
Zygomycosis	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—
Bone marrow failure	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—
Splenic infarction	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—	—
Pyrexia	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—
Asthenia	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—
Fatigue	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—
Mucosal inflammation	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—
Multi-organ failure	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—
Atrial fibrillation	Cardiac disorders	—	—	—	—	—	—	—	—	—	—	—	—	—

Other adverse events (226 terms — click to expand)

Reaction	System	Cohort 1: Milademetan 60 mg	Cohort 2: Milademetan 90 mg	Cohort 3: Milademetan 120 mg	Cohort 4: Milademetan 160 mg	Cohort 5: Milademetan 210 mg	Cohort 6b: Milademetan 160…	Cohort 7c: Milademetan 160…	Cohort 8d: Milademetan 160…	Cohort 9d: Milademetan 220…	Cohort 10e: Milademetan 16…	Cohort 11f: Milademetan 16…	Cohort 12e: Milademetan 20…	Cohort 13f: Milademetan 20…
Nausea	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—
Fatigue	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—
Oedema peripheral	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—
Hypokalaemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—	—	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—
Lung infection	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—	—
Pneumonia	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—	—	—	—	—	—
Hypomagnesaemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—
Neutropenia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—
Febrile neutropenia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—
Hypotension	Vascular disorders	—	—	—	—	—	—	—	—	—	—	—	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—
Pollakiuria	Renal and urinary disorders	—	—	—	—	—	—	—	—	—	—	—	—	—
Rash maculo-papular	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—
Dry mouth	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—
Haemorrhoids	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—
Oral disorder	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—
Toothache	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—
Asthenia	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—
Sepsis	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—	—
Bacteraemia	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—	—
Oral candidiasis	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—	—
Dehydration	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—	—	—	—	—	—
Hyperuricaemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—	—	—	—	—	—
Hyperphosphataemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—	—	—	—	—	—
Fluid overload	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—	—	—	—	—	—
Leukopenia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—

Most-reported serious reactions: Lung infection, Pneumonia, Sepsis, Febrile neutropenia, Death, Bacteraemia, Cellulitis, Pneumonia fungal.

Data from ClinicalTrials.gov NCT02319369 adverse events section.

Sponsor's own description

This study will take place in parts: * Dose Escalation (Part 1): Participants receive milademetan alone with different dose schedules * Dose Escalation (Part 1A): Participants receive milademetan in combination with 5-azacytidine (AZA), with different dose schedules The recommended dose for Part 2 will be selected. * Dose Expansion (Part 2): After Part 1A, participants will receive the recommended Part 2 dose schedule. There will be three groups - those with: 1. refractory or relapsed acute myelogenous leukemia (AML) 2. newly diagnosed AML unfit for intensive chemotherapy 3. high-risk myelodysplastic syndrome (MDS) * End-of-Study Follow-Up: Safety information will be collected until 30 days after the last treatment. This is the end of the study. The recommended dose for the next study will be selected.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

Targeting apoptosis in cancer therapy.
Carneiro BA, El-Deiry WS. · · 2020 · cited 1823× · PMID 32203277 · DOI 10.1038/s41571-020-0341-y
Targeting p53 pathways: mechanisms, structures, and advances in therapy.
Wang H, Guo M, Wei H, Chen Y. · · 2023 · cited 580× · PMID 36859359 · DOI 10.1038/s41392-023-01347-1
Recent advances in targeting the "undruggable" proteins: from drug discovery to clinical trials.
Xie X, Yu T, Li X, Zhang N, et al · · 2023 · cited 246× · PMID 37669923 · DOI 10.1038/s41392-023-01589-z
MDM2/X inhibitors under clinical evaluation: perspectives for the management of hematological malignancies and pediatric cancer.
Tisato V, Voltan R, Gonelli A, Secchiero P, et al · · 2017 · cited 191× · PMID 28673313 · DOI 10.1186/s13045-017-0500-5
Dysfunctional diversity of p53 proteins in adult acute myeloid leukemia: projections on diagnostic workup and therapy.
Prokocimer M, Molchadsky A, Rotter V. · · 2017 · cited 127× · PMID 28607134 · DOI 10.1182/blood-2017-02-763086
Inhibition of p53 inhibitors: progress, challenges and perspectives.
Sanz G, Singh M, Peuget S, Selivanova G. · · 2019 · cited 106× · PMID 31310659 · DOI 10.1093/jmcb/mjz075
The role of TP53 in acute myeloid leukemia: Challenges and opportunities.
Barbosa K, Li S, Adams PD, Deshpande AJ. · · 2019 · cited 93× · PMID 31393631 · DOI 10.1002/gcc.22796
MDM2 Inhibitors for Cancer Therapy: The Past, Present, and Future.
Wang W, Albadari N, Du Y, Fowler JF, et al · · 2024 · cited 85× · PMID 38697854 · DOI 10.1124/pharmrev.123.001026

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Verify against primary sources

ClinicalTrials.gov — authoritative US registry record
WHO ICTRP — international registry index
EU Clinical Trials Register
Sponsor press releases (Google)

Data sources for this page

Trial protocol + status: ClinicalTrials.gov NCT02319369 (US National Library of Medicine, public domain)
Publications: Europe PMC API search by NCT ID, retrieved 10 June 2026
Drug + disease cross-links: matched in real time against Drug Landscape's normalised drug + company + condition tables
Sponsor: as reported to ClinicalTrials.gov by Daiichi Sankyo
Last refreshed: 11 October 2021

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02319369.

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NCT02319369

Quick facts

Drugs / interventions tested

Conditions studied

Sponsor

Who can join

Results — posted to ClinicalTrials.gov

Adverse events — posted to ClinicalTrials.gov

Serious adverse events (53 terms)

Sponsor's own description

Publications & conference data

Related trials

Other trials of Milademetan

Other recruiting trials for Acute Myelogenous Leukemia

Other Daiichi Sankyo trials

Verify against primary sources