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Ornithine

Dose escalation of AMXT1501 with a fixed low dose of DFMO will follow a 3 + 3 dose escalation design. The AMXT 1501 starting dose administered in the first cohort will be 80 mg (2 capsules); each capsule contains 40 mg of active drug. The dose will be given orally, once daily, fasted state alone for 14 days, and starting on Day 15 AMXT 1501 80 mg given in combination with fixed low-dose oral DFMO at 250mg 2x per day (BID), for an additional 14 days; for a total 28 days of treatment per cycle. Cycle 2 includes AMXT1501 + DFMO that will be administered for 28 days. The patient can be treated for additional 28 day treatment cycles as deemed appropriate by their study investigator. Dose escalation of AMXT1501 alone will increase per Part 1 cohort.

Dose escalation of DFMO with the Part 1 AMXT1501 RP2D fixed dose will follow a 3 + 3 dose escalation design.

The AMXT 1501 starting dose administered in the first cohort will be one level below the AMXT 1501 Part 1 RP2D with 500 mg DFMO BID. The morning dose will be given orally of both AMXT1501 and DFMO, in a fasted state. The evening dose of DFMO alone will be given prior to bed-time for 28 days per cycle. The patient can be treated for additional 28 day treatment cycles as deemed appropriate by their study investigator. Dose escalation of DFMO alone will increase per Part 2 cohort.

The expansion cohort will include up to 14 evaluable patients at a proposed RP2D level of AMXT1501 and DFMO defined by Part 2 to further characterize safety at proposed RP2D dose level with repeat dosing, and characterize early anti-tumor activity.

AMXT 1501 dicaprate is D-lys(palmitoyl)-spermine dicaprate salt in 40 mg or 200 mg (free base content) enterically-coated capsules

AMXT1501

DFMO is DL-2-(difluoromethyl) ornithine monohydrochloride monohydrate 250 mg in hard gelatin capsules

DFMO

Nicole Gallegos, BS, MBA

Jackie Walling, MBChB PhD

A Phase 1 study will be conducted to establish safety and dose level of AMXT 1501 dicaprate alone, and in combination with DFMO, in cancer patients.

The objective of this study is to determine the safety and tolerability of oral AMXT 1501 dicaprate (AMXT1501) in combination with DFMO in patients with advanced solid tumors. Secondary objectives include characterization of plasma pharmacokinetics (PK) of AMXT 1501 as well as pharmacodynamic (PD) assessment of the impact of AMXT 1501 in combination with DFMO on polyamine uptake by circulating lymphocytes (blood cells).

To these aims, the study will evaluate the safety, PK and PD profiles of orally-administered AMXT 1501 and DFMO. Approximately, 52 patients will be enrolled to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of AMXT 1501 and DFMO in combination. The MTD is defined as the highest dose level below at which dose escalation is stopped.

Oral AMXT 1501 Dicaprate in Combination With DFMO

Phase I Dose-Finding, Safety Study of Oral AMXT 1501 Dicaprate and Difluoromethylornithine (DFMO) in Patients With Advanced Solid Tumors

To evaluate the effect AMXT1501 in combination therapy with DFMO on pharmacodynamic (PD) biomarker of polyamine uptake

To evaluate dose-limiting toxicities (DLTs) of AMXT 1501 in combination with DFMO, in patients with advanced cancer and to establish a recommended Phase 2 dose (RP2D)

To evaluate the safety and tolerability of AMXT1501 and DFMO combination

To evaluate the pharmacokinetics (PK) of AMXT 1501 alone and in combination with DFMO

To characterize Investigator defined Overall Response Rate (ORR) using RECIST v1.1 response criteria.

To characterize Investigator defined Duration of Response (DOR), using RECIST v1.1 response criteria and length of time (in days) from last study drug administration to time patient has progressive disease.

Evaluate the effects of treatment with AMXT1501 in combination with DFMO on the expression of immune related gene signatures, immune cell phenotype by IHC, AMXT1501 and DFMO drug levels impact on polyamine levels

Aminex Therapeutics, Inc.

Cohort will have a total 6 subjects: SAD (2 subjects receiving placebo and 4 subjects receiving active AMXT 1501 dicaprate);

SAD cohorts are defined as follows:

* Cohort 1: One placebo and one AMXT 1501 dicaprate subject will be treated as sentinel subjects receiving one tablet each of their assigned treatment. Assuming no intolerance is noted after at least 3 days, the remaining cohort subjects (placebo, 1 subject and AMXT 1501 dicaprate, 3 subjects) will be treated.
* Cohort 2: 2 subjects 2 placebo each and 4 subjects 2 AMXT 1501 dicaprate tablets each
* Cohort 3: 2 subjects 4 placebos each and 4 subjects 4 AMXT 1501 dicaprate tablets each
* Cohort 4: 2 subjects 8 placebos each and 4 subjects 8 AMXT 1501 dicaprate tablets each

Each cohort will have a total 6 subjects: MAD (2 subjects receiving placebo and 4 subjects receiving active AMXT 1501 dicaprate); MAD cohorts will receive dosing once daily for 14 consecutive days. Dosing will be contingent on adequate tolerance in Cohorts 1-5.

* Cohort 6: 2 subjects 2 placebos each; 4 subjects 2 AMXT 1501 dicaprate tablets each
* Cohort 7: 2 subjects 4 placebos each; 4 subjects 4 AMXT 1501 dicaprate tablets each
* Cohort 8: 2 subjects 8 placebos each; 4 subjects 8 AMXT 1501 dicaprate tablets each

Each cohort will have a total 6 subjects: FE crossover (6 subjects receiving active AMXT 1501 dicaprate).

FE Crossover:

• Cohort 5: 6 new subjects will be randomized to a fed (n=3 standard meal) or fasted (n=3) group and administered the highest dose of AMXT 1501 dicaprate tolerated by previous cohorts. First dose and accompanying assessments will be referred to as Period 1. Subjects will then crossover to the opposite diet plan (fed or fasted) and receive a second administration of study treatment at the same dose level. The second dose and assessments are referred to as Period 2. There will be a 7-day washout between doses administered in Periods 1 and 2.

Study treatment will be provided in tablet form; each containing 128 mg AMXT 1501 dicaprate salt, 80 mg of which is AMXT 1501 freebase (active drug), plus excipients and are orally administered.

AMXT 1501

Reference Therapy, Dose and Route of Administration:

Placebo Tablets, orally administered

Placebo Oral Tablet

This is a Phase 1 study, which will assess the safety, PK, and pharmacodynamics (PD) of orally-administered AMXT 1501 dicaprate in normal healthy male volunteers.

The study is comprised of a total of 8 cohorts; 4 single ascending dose (SAD) cohorts, 1 Food Effect (FE) Crossover cohort, and 3 multiple ascending dose (MAD) cohorts. Tablets will be administered after an overnight fast (10 hours) with at least 250 mL water. No food will be administered (exception for "fed" subjects, see below) for one hour thereafter.

Each cohort will have a total 6 subjects: SAD and MAD (2 subjects receiving placebo and 4 subjects receiving active AMXT 1501 dicaprate); and FE crossover (6 subjects receiving active AMXT 1501 dicaprate).

The Phase 1 study, which will assess the safety, PK, and pharmacodynamics (PD) of orally-administered AMXT 1501 dicaprate in normal healthy male volunteers.

The study is comprised of a total of 8 cohorts; 4 single ascending dose (SAD) cohorts, 1 Food Effect (FE) Crossover cohort, and 3 multiple ascending dose (MAD) cohorts. Tablets will be administered after an overnight fast (10 hours) with at least 250 mL water. No food will be administered (exception for "fed" subjects, see below) for one hour thereafter.

Each cohort will have a total 6 subjects: SAD and MAD (2 subjects receiving placebo and 4 subjects receiving active AMXT 1501 dicaprate); and FE crossover (6 subjects receiving active AMXT 1501 dicaprate).

SAD cohorts are defined as follows:

* Cohort 1: One placebo and one AMXT 1501 dicaprate subject will be treated as sentinel subjects receiving one tablet each of their assigned treatment. Assuming no intolerance is noted after at least 3 days, the remaining cohort subjects (placebo, 1 subject and AMXT 1501 dicaprate, 3 subjects) will be treated.
* Cohort 2: 2 subjects 2 placebo each and 4 subjects 2 AMXT 1501 dicaprate tablets each
* Cohort 3: 2 subjects 4 placebos each and 4 subjects 4 AMXT 1501 dicaprate tablets each
* Cohort 4: 2 subjects 8 placebos each and 4 subjects 8 AMXT 1501 dicaprate tablets each

FE Crossover:

• Cohort 5: 6 new subjects will be randomized to a fed (n=3 standard meal) or fasted (n=3) group and administered one dose lower of the maximum tolerated AMXT 1501 dose in the previous SAD cohorts. First dose and accompanying assessments will be referred to as Period 1. Subjects will then crossover to the opposite diet plan (fed or fasted) and receive a second administration of study treatment at the same dose level. The second dose and assessments are referred to as Period 2. There will be a 7-day washout between doses administered in Periods 1 and 2.

MAD cohorts will receive dosing once daily for 14 consecutive days. Dosing will be contingent on adequate tolerance in Cohorts 1-5.

* Cohort 6: 2 subjects 2 placebos each; 4 subjects 2 AMXT 1501 dicaprate tablets each
* Cohort 7: 2 subjects 4 placebos each; 4 subjects 4 AMXT 1501 dicaprate tablets each
* Cohort 8: 2 subjects 8 placebos each; 4 subjects 8 AMXT 1501 dicaprate tablets each

The study is comprised of a total of 8 cohorts; 4 single ascending dose (SAD) cohorts, 1 Food Effect (FE) Crossover cohort, and 3 multiple ascending dose (MAD) cohorts. Tablets will be administered after an overnight fast (10 hours) with at least 250 mL water. No food will be administered (exception for "fed" subjects, see below) for one hour thereafter.

Each cohort will have a total 6 subjects: SAD and MAD (2 subjects receiving placebo and 4 subjects receiving active AMXT 1501 dicaprate); and FE crossover (6 subjects receiving active AMXT 1501 dicaprate).

If subject is given active drug or placebo is masked

Study of Orally-Administered AMXT 1501 Dicaprate in Normal Healthy Volunteers

Phase 1 Double-Blind, Placebo Controlled, Dose-Escalation Safety, Pharmacokinetic and Pharmacodynamic Study of Orally-Administered AMXT 1501 Dicaprate in Normal Healthy Volunteers

Determine the maximum feasible dose (MFD) of single and multiple doses of oral AMXT 1501 dicaprate in normal healthy volunteers.

Determine the pharmacokinetics (PK) of single and multiple doses of oral AMXT 1501 dicaprate in normal subjects, by using Area under the plasma concentration versus time curve (AUC)

Determine the pharmacokinetics (PK) of single and multiple doses of oral AMXT 1501 dicaprate in normal subjects, by using Peak Plasma Concentration (Cmax)

Assess influence of food on the PK of single doses of AMXT 1501 dicaprate, by comparing Area under the plasma concentration versus time curve (AUC)

Assess influence of food on the PK of single doses of AMXT 1501 dicaprate, by comparing Peak Plasma Concentration (Cmax)

To assess the effects of oral AMXT 1501 by testing for the appropriate level of the drug measured by the biomarker Use the biomarker test level to determine the recommended AMXT1501 Phase 2 dose.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Oral AMXT 1501 Dicaprate in Combination With DFMO	NCT03536728	Cancer Solid Tumor Solid Carcinoma Advanced Cancer	AMXT1501 DFMO	12 Years -	Aminex Therapeutics, Inc.
Study of Orally-Administered AMXT 1501 Dicaprate in Normal Healthy Volunteers	NCT03077477	Neoplasms Medication Toxi... Tolerance	AMXT 1501 Placebo Oral Ta...	18 Years - 55 Years	Aminex Therapeutics, Inc.
Oral AMXT 1501 Dicaprate in Combination With DFMO	NCT03536728	Cancer Solid Tumor Solid Carcinoma Advanced Cancer	AMXT1501 DFMO	12 Years -	Aminex Therapeutics, Inc.

Spots Global Cancer Trial Database for amxt 1501

Every month we try and update this database with for amxt 1501 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for amxt 1501

Every month we try and update this database with for amxt 1501 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for amxt 1501 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.