Clincosm LogoSign in Get a demo

Phase 1/2A Study of TRC253, an Androgen Receptor Antagonist, in Metastatic Castration-resistant Prostate Cancer Patients

Sponsor
Tracon Pharmaceuticals Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT02987829
Collaborator
Janssen Pharmaceutica N.V., Belgium (Industry)
72
Enrollment
5
Locations
6
Arms
41.6
Actual Duration (Months)
14.4
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a multi-center, first-in-human, open-label, Phase 1/2A dose-escalation study in which eligible patients with metastatic castration-resistant prostate carcinoma (mCRPC) will receive oral doses of TRC253. The study will be conducted in 2 parts: part 1 (dose escalation) and part 2 (dose expansion).

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Detailed Description

The patient population consists of men ≥18 years of age with adenocarcinoma of the prostate with metastatic disease. Patients who have not undergone orchiectomy must have serum testosterone levels <50 ng/dL determined within 4 weeks prior to start of study drug, and, if applicable, must have discontinued treatment with first or second generation anti-androgens as specified in the inclusion criteria.

During Part 1 of the study, patients will be assigned sequentially to increasing TRC253 doses. The starting dose of TRC253 is 40 mg once daily, orally. TRC253 doses will be escalated in subsequent cohorts after all patients enrolled in a given cohort have completed the 28-day dose-limiting toxicity (DLT) evaluation period. Dose escalation in Part 1 will follow single-patient dose escalation design until drug-related toxicity occurs. When an initial drug-related toxicity occurs or DLT in a single patient the cohort will be expanded according to 3+3 design rules. Subsequent dose levels will enroll patients based on 3+3 design. At the maximum tolerated dose (MTD) or minimum efficacious dose (MED), up to twelve patients may be enrolled.

Part 2 will consist of two cohorts of initially up to 30 patients (Cohort 1) and up to 30 patients (Cohort 2) to receive TRC253 at the recommended Phase 2 dose (RP2D). The objective of Part 2 is to gather additional information on the safety, pharmacokinetics (PK) and pharmacodynamic (PD) characteristics, and the clinical efficacy of TRC253 in a pre-defined population of patients with metastatic castrate-resistant prostate cancer (mCRPC). Patients enrolled into Part 2 will have received prior treatment with enzalutamide or apalutamide and showed characteristics of acquired resistance based on changes in PSA serum levels. Patients will be centrally screened for the presence of the AR F876L (androgen receptor F876L) mutation from a plasma sample and enrolled into Cohort 1 (AR F876L positive) or Cohort 2 (AR F876L negative). Cohort 2 may be expanded if a specific molecular mechanism sensitizing the mCRPC to TRC253 therapy can be identified retrospectively. Additional patients may be prospectively selected for this specific molecular resistance mechanism and added to Cohort 2 upon recommendation by the medical monitor and Principal Investigators.

Study Design

Study Type:
Interventional
Actual Enrollment :
72 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-label Phase 1/2A Study To Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of TRC253, an Androgen Receptor Antagonist, in Patients With Metastatic Castration-resistant Prostate Cancer
Actual Study Start Date :
May 23, 2017
Actual Primary Completion Date :
Oct 6, 2019
Actual Study Completion Date :
Nov 9, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: Dose Level 1: TRC253 40 mg daily

40 mg of single-agent TRC253 to be administered as oral capsules once daily

Drug: TRC253
TRC253 is a high-affinity, small molecule antagonist of the androgen receptor (AR) with inhibitory activity against wild type AR and specific mutated variants of AR. TRC253 blocks AR nuclear translocation as well as AR binding to DNA and is an antagonist of transcription for wild type AR and mutated AR. TRC253 is orally active and does not have agonist activity towards either the wild type or mutated ARs. TRC253 treatment in the Hershberger assay results in complete inhibition of androgen sensitive organ development. TRC253 is efficacious in an LNCaP xenograft model driven by F876L (also known as F877L) mutant AR.
Other Names:
  • AR Antagonist

    		•
    Experimental: Dose Level 2: TRC253 80 mg

    80 mg of single-agent TRC253 to be administered as oral capsules once daily

    Drug: TRC253
    TRC253 is a high-affinity, small molecule antagonist of the androgen receptor (AR) with inhibitory activity against wild type AR and specific mutated variants of AR. TRC253 blocks AR nuclear translocation as well as AR binding to DNA and is an antagonist of transcription for wild type AR and mutated AR. TRC253 is orally active and does not have agonist activity towards either the wild type or mutated ARs. TRC253 treatment in the Hershberger assay results in complete inhibition of androgen sensitive organ development. TRC253 is efficacious in an LNCaP xenograft model driven by F876L (also known as F877L) mutant AR.
    Other Names:
  • AR Antagonist

    		•
    Experimental: Dose Level 3: TRC253 160 mg

    160 mg of single-agent TRC253 to be administered as oral capsules once daily

    Drug: TRC253
    TRC253 is a high-affinity, small molecule antagonist of the androgen receptor (AR) with inhibitory activity against wild type AR and specific mutated variants of AR. TRC253 blocks AR nuclear translocation as well as AR binding to DNA and is an antagonist of transcription for wild type AR and mutated AR. TRC253 is orally active and does not have agonist activity towards either the wild type or mutated ARs. TRC253 treatment in the Hershberger assay results in complete inhibition of androgen sensitive organ development. TRC253 is efficacious in an LNCaP xenograft model driven by F876L (also known as F877L) mutant AR.
    Other Names:
  • AR Antagonist

    		•
    Experimental: Dose Level 4: TRC253 240 mg

    240 mg of single-agent TRC253 to be administered as oral capsules once daily

    Drug: TRC253
    TRC253 is a high-affinity, small molecule antagonist of the androgen receptor (AR) with inhibitory activity against wild type AR and specific mutated variants of AR. TRC253 blocks AR nuclear translocation as well as AR binding to DNA and is an antagonist of transcription for wild type AR and mutated AR. TRC253 is orally active and does not have agonist activity towards either the wild type or mutated ARs. TRC253 treatment in the Hershberger assay results in complete inhibition of androgen sensitive organ development. TRC253 is efficacious in an LNCaP xenograft model driven by F876L (also known as F877L) mutant AR.
    Other Names:
  • AR Antagonist

    		•
    Experimental: Dose Level 5: TRC253 280 mg

    280 mg of single-agent TRC253 to be administered as oral capsules once daily

    Drug: TRC253
    TRC253 is a high-affinity, small molecule antagonist of the androgen receptor (AR) with inhibitory activity against wild type AR and specific mutated variants of AR. TRC253 blocks AR nuclear translocation as well as AR binding to DNA and is an antagonist of transcription for wild type AR and mutated AR. TRC253 is orally active and does not have agonist activity towards either the wild type or mutated ARs. TRC253 treatment in the Hershberger assay results in complete inhibition of androgen sensitive organ development. TRC253 is efficacious in an LNCaP xenograft model driven by F876L (also known as F877L) mutant AR.
    Other Names:
  • AR Antagonist

    		•
    Experimental: Dose Level 6: TRC253 320 mg

    320 mg of single-agent TRC253 to be administered as oral capsules once daily

    Drug: TRC253
    TRC253 is a high-affinity, small molecule antagonist of the androgen receptor (AR) with inhibitory activity against wild type AR and specific mutated variants of AR. TRC253 blocks AR nuclear translocation as well as AR binding to DNA and is an antagonist of transcription for wild type AR and mutated AR. TRC253 is orally active and does not have agonist activity towards either the wild type or mutated ARs. TRC253 treatment in the Hershberger assay results in complete inhibition of androgen sensitive organ development. TRC253 is efficacious in an LNCaP xenograft model driven by F876L (also known as F877L) mutant AR.
    Other Names:
  • AR Antagonist

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of Patients Who Experience Dose Limiting Toxicities by Dose Level [5 weeks]

      The trial began with single patient dose escalation rules. If 1 of 1 patients at a given dose experienced a DLT, the study transitioned to a 3+3 design. If 1 of 3 patients experienced a DLT, the dose level was expanded to 6 patients. The maximum tolerated dose (MTD) would have been exceeded if ≥ 33% of patients experience DLT at a given dose level. DLT occurred when a patient had 1 or more toxicities outlined in the protocol that was considered at least possibly related to TRC253 during the first 5 weeks of study participation in the trial. In addition, any dose level could be expanded to further explore PK (the target PK concentration associated with activity in preclinical models was 335 ng/mL). The number of DLTs by dose cohort have been presented.

    Secondary Outcome Measures

    1. Number of Participants With a Serum Prostate-specific Antigen (PSA) Response According to Prostate Cancer Working Group (PCWG3) Criteria [12 weeks]

      Serum prostate-specific antigen (PSA) response according to Prostate Cancer Working Group (PCWG3) criteria is defined as at least a 50% decrease in PSA from baseline confirmed at least 4 weeks later

    2. Maximum Change in QTcF [18 months]

      Maximum change in QTcF from baseline by dose level

    3. Percent Change From Baseline in Standard Uptake Value (SUV) to Assess TRC253 Receptor Occupancy [4 Weeks]

      To confirm the recommended phase 2 dose (RP2D), patients at select dose levels will undergo positron emission tomography scan (PET) scans using fluoro-5alpha-dihydrotestosterone (FDHT), a radiopharmaceutical specifically designed to image binding to androgen receptor (AR). Imaging occurred at one center under their existing investigational new drug application (IND) and institutional protocol. A negative change from baseline in the standard uptake value indicate a decrease in metabolic activity of the tumor and indicate increased receptor occupancy of TRC253.

    4. Median Time to Progression by Dose Level [18 months]

      Preliminary anti-tumor effects of TRC253 as assessed by median time to progression by Prostate Cancer Working Group 3 (PCWG3) criteria by dose level

    5. Number of Patients Who Achieved the Target Concentration of TRC253 at Steady State [28 days]

      Determine the number of patients who achieved the target concentration of TRC253 at steady state (target efficacy concentration of 335 ng/mL based on preclinical models).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 99 Years
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. Must have received at least 2 prior therapies approved for CRPC; including a prior AR inhibitor (e.g., enzalutamide or apalutamide). (Part 1 only)

    2. Must have received enzalutamide or apalutamide. (Note: additional therapies approved for CRPC prior to enzalutamide or apalutamide are allowed.) (Part 2 only)

    3. Must have shown clinical characteristics of acquired resistance to enzalutamide or apalutamide defined as: decline in serum PSA ≥50% compared to baseline serum levels by week 12 (±4 weeks) of enzalutamide or apalutamide treatment and before disease progression by PCWG3 PSA criteria, OR disease progression by PCWG3 radiographic criteria. (Part 2 only)

    Parts 1 and 2:

    1. Histologically confirmed adenocarcinoma of the prostate with metastatic disease.

    2. Male ≥18 years of age.

    3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

    4. Prior orchiectomy or serum testosterone levels <50 ng/dL determined within 4 weeks prior to start of study drug.

    5. Adequate baseline organ function.

    6. Ongoing androgen depletion therapy with a gonadotropin-releasing hormone (GnRH) analog or inhibitor, or orchiectomy (i.e., surgical or medical castration). Note: patients who have not undergone orchiectomy must continue GnRH analog therapy for the duration of this protocol.

    7. For patients previously treated with first generation anti-androgens (i.e., flutamide, nilutamide, or bicalutamide), discontinuation of flutamide or nilutamide therapy must occur >4 weeks (>6 weeks for bicalutamide) prior to start of study drug with no evidence of an anti-androgen withdrawal response (i.e., no decline in serum PSA).

    8. For patients previously treated with chemotherapy, targeted therapy, immunotherapy, or treatment with an investigational anticancer agent, discontinuation must have occurred ≥2 weeks, or after at least 4 half-lives, whichever is longer, prior to study drug administration. For enzalutamide and apalutamide, the washout period will be at least 3 weeks prior to start of study drug with no evidence of an anti-androgen withdrawal response (i.e., no decline in serum PSA).

    9. For patients previously treated with other agents approved for the treatment of prostate cancer (5-α reductase inhibitors, estrogens, others), discontinuation of therapy must have occurred ≥4 weeks prior to start of study drug.

    10. Palliative radiotherapy (to bone or soft tissue lesions) must be completed >2 weeks prior to start of study drug.

    11. For patients receiving bone-loss prevention treatment (e.g., bisphosphonates or denosumab), the patient must be on stable dose ≥4 weeks prior to start of study drug.

    12. A man who is sexually active with a woman of childbearing potential must agree to use a barrier method of birth control during the study and for 4 weeks after receiving the last dose of study drug. All men must also not donate sperm during the study and for 90 days after receiving the last dose of study drug.

    13. Patient must be willing and able to adhere to the prohibitions and restrictions specified in this protocol.

    14. Each patient must sign an informed consent form (ICF) indicating that he understands the purpose of and procedures required for the study and is willing to participate in the study. Consent is to be obtained prior to the initiation of any study-related tests or procedures that are not part of standard-of-care for the patient's disease.

    Exclusion Criteria:

    1. History of seizures.

    2. Previously documented or current brain metastases.

    3. Untreated spinal cord compression.

    4. Positive test result for human immunodeficiency virus.

    5. History of clinically significant cardiovascular disease including.

    6. Active or chronic hepatitis B or hepatitis C as demonstrated by hepatitis B surface antigen positivity and/or anti- hepatitis C virus positivity, respectively. Patients with clinically active or chronic liver disease, including liver cirrhosis of Child-Pugh class C, are also excluded.

    7. Second primary malignancy that has not been in remission for greater than 3 years. Exceptions that do not require a 3 year remission include: related non-melanoma skin cancer or resected melanoma in situ.

    8. Any serious underlying medical or psychiatric condition (e.g., alcohol or drug abuse), dementia or altered mental status or any issue that would impair the ability of the patient to receive or tolerate the planned treatment, to understand informed consent or that in the opinion of the investigator would contraindicate the patient's participation in the study or that would confound the results of the study.

    9. Evidence of active viral, bacterial, or systemic fungal infection requiring systemic treatment within 7 days prior to the first dose of study drug. Patients requiring any systemic antiviral, antifungal, or antibacterial therapy for active infection must have completed treatment no less than 7 days prior to the first dose of study drug.

    10. Known allergies, hypersensitivity, or intolerance to TRC253 or its excipients.

    11. Enrollment in another interventional study.

    12. Major surgery (e.g., requiring general anesthesia) within 3 weeks before screening, or has not fully recovered from prior surgery (i.e., unhealed wound), or surgery planned during the time the patient is expected to participate in the study. Note: patients with planned surgical procedures to be conducted under local anesthesia may participate.

    13. Plan to father a child while enrolled in this study or within 90 days after the last dose of study drug.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Alabama at Birmingham Birmingham Alabama United States 35233
    2 Honor Health Scottsdale Arizona United States 85258
    3 University of California at Los Angeles Santa Monica California United States 90404
    4 Memorial Sloan Kettering Cancer Center New York New York United States 10065
    5 University of Utah Salt Lake City Utah United States 84112

    Sponsors and Collaborators

    • Tracon Pharmaceuticals Inc.
    • Janssen Pharmaceutica N.V., Belgium

    Investigators

    • Study Director: James Freddo, MD, Tracon Pharmaceuticals Inc.

    Study Documents (Full-Text)

    More Information

    Publications

    Responsible Party:
    Tracon Pharmaceuticals Inc.
    ClinicalTrials.gov Identifier:
    NCT02987829
    Other Study ID Numbers:
    • 253PC101
    First Posted:
    Dec 9, 2016
    Last Update Posted:
    Apr 23, 2021
    Last Verified:
    Mar 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Prostatic Neoplasms
    Androgen Receptor Antagonists

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title 40 mg TRC253/Daily 80 mg TRC253/Daily 160 mg TRC253/Daily 240 mg TRC253/Daily 280 mg TRC253/Daily 320 mg TRC253/Daily
    Arm/Group Description Single-agent TRC253 to be administered as oral capsules once daily. Single-agent TRC253 to be administered as oral capsules once daily. Single-agent TRC253 to be administered as oral capsules once daily. Single-agent TRC253 to be administered as oral capsules once daily. Single-agent TRC253 to be administered as oral capsules once daily. Single-agent TRC253 to be administered as oral capsules once daily.
    Period Title: Overall Study
    STARTED 1 1 2 7 51 10
    COMPLETED 1 1 2 7 51 10
    NOT COMPLETED 0 0 0 0 0 0

    Baseline Characteristics

    Arm/Group Title 40 mg TRC253/Daily 80 mg TRC253/Daily 160 mg TRC253/Daily 240 mg TRC253/Daily 280 mg TRC253/Daily 320 mg TRC253/Daily Total
    Arm/Group Description Single-agent TRC253 to be administered as oral capsules once daily. Single-agent TRC253 to be administered as oral capsules once daily. Single-agent TRC253 to be administered as oral capsules once daily. Single-agent TRC253 to be administered as oral capsules once daily. Single-agent TRC253 to be administered as oral capsules once daily. Single-agent TRC253 to be administered as oral capsules once daily. Total of all reporting groups
    Overall Participants 1 1 2 7 51 10 72
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    0
    0%
    0
    0%
    0
    0%
    2
    28.6%
    12
    23.5%
    5
    50%
    19
    26.4%
    >=65 years
    1
    100%
    1
    100%
    2
    100%
    5
    71.4%
    39
    76.5%
    5
    50%
    53
    73.6%
    Age (Years) [Mean (Full Range) ]
    Mean (Full Range) [Years]
    80
    65
    78
    68
    73
    67
    72
    Sex: Female, Male (Count of Participants)
    Female
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Male
    1
    100%
    1
    100%
    2
    100%
    7
    100%
    51
    100%
    10
    100%
    72
    100%
    Race/Ethnicity, Customized (Count of Participants)
    Asian
    0
    0%
    0
    0%
    0
    0%
    1
    14.3%
    2
    3.9%
    0
    0%
    3
    4.2%
    Black or African American
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    5
    9.8%
    3
    30%
    8
    11.1%
    White
    1
    100%
    1
    100%
    1
    50%
    6
    85.7%
    42
    82.4%
    6
    60%
    57
    79.2%
    Other (Patient declined to answer)
    0
    0%
    0
    0%
    1
    50%
    0
    0%
    2
    3.9%
    1
    10%
    4
    5.6%
    Region of Enrollment (participants) [Number]
    United States
    1
    100%
    1
    100%
    2
    100%
    7
    100%
    51
    100%
    10
    100%
    72
    100%

    Outcome Measures

    1. Primary Outcome
    Title Number of Patients Who Experience Dose Limiting Toxicities by Dose Level
    Description The trial began with single patient dose escalation rules. If 1 of 1 patients at a given dose experienced a DLT, the study transitioned to a 3+3 design. If 1 of 3 patients experienced a DLT, the dose level was expanded to 6 patients. The maximum tolerated dose (MTD) would have been exceeded if ≥ 33% of patients experience DLT at a given dose level. DLT occurred when a patient had 1 or more toxicities outlined in the protocol that was considered at least possibly related to TRC253 during the first 5 weeks of study participation in the trial. In addition, any dose level could be expanded to further explore PK (the target PK concentration associated with activity in preclinical models was 335 ng/mL). The number of DLTs by dose cohort have been presented.
    Time Frame 5 weeks

    Outcome Measure Data

    Analysis Population Description
    All patients who received at least a portion of a dose of TRC253 are included in the analysis.
    Arm/Group Title 40 mg TRC253/Daily 80 mg TRC253/Daily 160 mg TRC253/Daily 240 mg TRC253/Daily 280 mg TRC253/Daily 320 mg TRC253/Daily
    Arm/Group Description Single-agent TRC253 to be administered as oral capsules once daily. Single-agent TRC253 to be administered as oral capsules once daily. Single-agent TRC253 to be administered as oral capsules once daily. Single-agent TRC253 to be administered as oral capsules once daily. Single-agent TRC253 to be administered as oral capsules once daily. Single-agent TRC253 to be administered as oral capsules once daily.
    Measure Participants 1 1 2 7 51 10
    Count of Participants [Participants]
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    10%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection 280 mg TRC253/Daily
    Comments Determination of the maximum tolerated dose.
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Other Statistical Analysis One dose limiting toxicity occurred at 320 mg daily of grade 3 QTc prolongation therefore the 280 mg dose was determined to be the maximum tolerated dose and selected as the phase 2 dose.
    2. Secondary Outcome
    Title Number of Participants With a Serum Prostate-specific Antigen (PSA) Response According to Prostate Cancer Working Group (PCWG3) Criteria
    Description Serum prostate-specific antigen (PSA) response according to Prostate Cancer Working Group (PCWG3) criteria is defined as at least a 50% decrease in PSA from baseline confirmed at least 4 weeks later
    Time Frame 12 weeks

    Outcome Measure Data

    Analysis Population Description
    Patients with a baseline PSA and at least 1 on study PSA that were confirmed at least 4 weeks later.
    Arm/Group Title 40 mg TRC253/Daily 80 mg TRC253/Daily 160 mg TRC253/Daily 240 mg TRC253/Daily 280 mg TRC253/Daily 320 mg TRC253/Daily
    Arm/Group Description Single-agent TRC253 to be administered as oral capsules once daily. Single-agent TRC253 to be administered as oral capsules once daily. Single-agent TRC253 to be administered as oral capsules once daily. Single-agent TRC253 to be administered as oral capsules once daily. Single-agent TRC253 to be administered as oral capsules once daily. Single-agent TRC253 to be administered as oral capsules once daily.
    Measure Participants 1 1 2 7 51 10
    Count of Participants [Participants]
    0
    0%
    0
    0%
    1
    50%
    0
    0%
    3
    5.9%
    1
    10%
    3. Secondary Outcome
    Title Maximum Change in QTcF
    Description Maximum change in QTcF from baseline by dose level
    Time Frame 18 months

    Outcome Measure Data

    Analysis Population Description
    Patients who received at least a portion of a dose of TRC253 with a baseline ECG and at least 1 on study ECG.
    Arm/Group Title 40 mg TRC253/Daily 80 mg TRC253/Daily 160 mg TRC253/Daily 240 mg TRC253/Daily 280 mg TRC253/Daily 320 mg TRC253/Daily
    Arm/Group Description Single-agent TRC253 to be administered as oral capsules once daily. Single-agent TRC253 to be administered as oral capsules once daily. Single-agent TRC253 to be administered as oral capsules once daily. Single-agent TRC253 to be administered as oral capsules once daily. Single-agent TRC253 to be administered as oral capsules once daily. Single-agent TRC253 to be administered as oral capsules once daily.
    Measure Participants 1 0 1 7 50 8
    Mean (Full Range) [msec]
    9
    22
    44.62
    37.56
    42.63
    4. Secondary Outcome
    Title Percent Change From Baseline in Standard Uptake Value (SUV) to Assess TRC253 Receptor Occupancy
    Description To confirm the recommended phase 2 dose (RP2D), patients at select dose levels will undergo positron emission tomography scan (PET) scans using fluoro-5alpha-dihydrotestosterone (FDHT), a radiopharmaceutical specifically designed to image binding to androgen receptor (AR). Imaging occurred at one center under their existing investigational new drug application (IND) and institutional protocol. A negative change from baseline in the standard uptake value indicate a decrease in metabolic activity of the tumor and indicate increased receptor occupancy of TRC253.
    Time Frame 4 Weeks

    Outcome Measure Data

    Analysis Population Description
    TRC253 4 week FDHT-PET response mean SUV based on the 5 hottest lesions (uncorrected)
    Arm/Group Title 40 mg TRC253/Daily 80 mg TRC253/Daily 160 mg TRC253/Daily 240 mg TRC253/Daily 280 mg TRC253/Daily 320 mg TRC253/Daily
    Arm/Group Description Single-agent TRC253 to be administered as oral capsules once daily. Single-agent TRC253 to be administered as oral capsules once daily. Single-agent TRC253 to be administered as oral capsules once daily. Single-agent TRC253 to be administered as oral capsules once daily. Single-agent TRC253 to be administered as oral capsules once daily. Single-agent TRC253 to be administered as oral capsules once daily.
    Measure Participants 0 0 1 2 1 2
    Mean (Full Range) [Percent Change from Baseline]
    -34.1
    -2.81
    27.78
    -45.88
    5. Secondary Outcome
    Title Median Time to Progression by Dose Level
    Description Preliminary anti-tumor effects of TRC253 as assessed by median time to progression by Prostate Cancer Working Group 3 (PCWG3) criteria by dose level
    Time Frame 18 months

    Outcome Measure Data

    Analysis Population Description
    In order to be eligible for efficacy analysis patients must have had a baseline CT scan and at least 1 on study CT scan.
    Arm/Group Title 40 mg TRC253/Daily Dose Levels Combined 80 mg TRC253/Daily Dose Levels Combined 160 mg TRC253/Daily Dose Levels Combined 240 mg TRC253/Daily 280 mg TRC253/Daily 320 mg TRC253/Daily
    Arm/Group Description Single-agent TRC253 to be administered as oral capsules once daily. Single-agent TRC253 to be administered as oral capsules once daily. Single-agent TRC253 to be administered as oral capsules once daily. Single-agent TRC253 to be administered as oral capsules once daily. Single-agent TRC253 to be administered as oral capsules once daily. Single-agent TRC253 to be administered as oral capsules once daily.
    Measure Participants 1 1 2 7 44 8
    Median (95% Confidence Interval) [months]
    8.7
    9.5
    4.8
    3.75
    4.64
    12.20
    6. Secondary Outcome
    Title Number of Patients Who Achieved the Target Concentration of TRC253 at Steady State
    Description Determine the number of patients who achieved the target concentration of TRC253 at steady state (target efficacy concentration of 335 ng/mL based on preclinical models).
    Time Frame 28 days

    Outcome Measure Data

    Analysis Population Description
    Patients who received at least 75% of planned continuous daily dosing after 28 days of daily dosing enrolled in part 1 of the study.
    Arm/Group Title 40 mg TRC253/Daily 80 mg TRC253/Daily 160 mg TRC253/Daily 240 mg TRC253/Daily 280 mg TRC253/Daily 320 mg TRC253/Daily
    Arm/Group Description Single-agent TRC253 to be administered as oral capsules once daily. Single-agent TRC253 to be administered as oral capsules once daily. Single-agent TRC253 to be administered as oral capsules once daily. Single-agent TRC253 to be administered as oral capsules once daily. Single-agent TRC253 to be administered as oral capsules once daily. Single-agent TRC253 to be administered as oral capsules once daily.
    Measure Participants 1 1 2 7 4 6
    Count of Participants [Participants]
    0
    0%
    0
    0%
    0
    0%
    4
    57.1%
    4
    7.8%
    5
    50%

    Adverse Events

    Time Frame 18 months
    Adverse Event Reporting Description Duration of participation +28 days
    Arm/Group Title 40 mg TRC253/Daily 80 mg TRC253/Daily 160 mg TRC253/Daily 240 mg TRC253/Daily 280 mg TRC253/Daily 320 mg TRC253/Daily
    Arm/Group Description Single-agent TRC253 to be administered as oral capsules once daily. Single-agent TRC253 to be administered as oral capsules once daily. Single-agent TRC253 to be administered as oral capsules once daily. Single-agent TRC253 to be administered as oral capsules once daily. Single-agent TRC253 to be administered as oral capsules once daily. Single-agent TRC253 to be administered as oral capsules once daily.
    All Cause Mortality
    40 mg TRC253/Daily 80 mg TRC253/Daily 160 mg TRC253/Daily 240 mg TRC253/Daily 280 mg TRC253/Daily 320 mg TRC253/Daily
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Serious Adverse Events
    40 mg TRC253/Daily 80 mg TRC253/Daily 160 mg TRC253/Daily 240 mg TRC253/Daily 280 mg TRC253/Daily 320 mg TRC253/Daily
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/1 (0%) 1/1 (100%) 1/2 (50%) 2/7 (28.6%) 13/51 (25.5%) 3/10 (30%)
    Blood and lymphatic system disorders
    Anaemia 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/7 (14.3%) 0/51 (0%) 0/10 (0%)
    Gastrointestinal disorders
    Abdominal Pain 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Rectal haemorrhage 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 0/51 (0%) 1/10 (10%)
    Vomiting 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    General disorders
    Disease progression 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Infections and infestations
    Pneumonia 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/7 (0%) 0/51 (0%) 0/10 (0%)
    Device related infection 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/7 (14.3%) 0/51 (0%) 0/10 (0%)
    Oesophageal candidiasis 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Oral candidiasis 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Pyelonephritis acute 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Urinary tract infection 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 2/51 (3.9%) 0/10 (0%)
    Injury, poisoning and procedural complications
    Hip fracture 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Overdose 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Metabolism and nutrition disorders
    Failure to thrive 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Hypercalcaemia 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Hyperglycaemia 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Musculoskeletal and connective tissue disorders
    Neck Pain 0/1 (0%) 1/1 (100%) 0/2 (0%) 0/7 (0%) 0/51 (0%) 0/10 (0%)
    Osteonecrosis 0/1 (0%) 1/1 (100%) 0/2 (0%) 0/7 (0%) 0/51 (0%) 0/10 (0%)
    Musculoskeletal pain 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 0/51 (0%) 1/10 (10%)
    Back pain 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 0/51 (0%) 1/10 (10%)
    Arthralgia 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 0/51 (0%) 1/10 (10%)
    Bone pain 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Meningeal neoplasm 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Nervous system disorders
    Spinal cord compression 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 2/51 (3.9%) 0/10 (0%)
    Renal and urinary disorders
    Acute kidney injury 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Urinary tract obstruction 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Respiratory, thoracic and mediastinal disorders
    Epistaxis 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/7 (14.3%) 0/51 (0%) 0/10 (0%)
    Dyspnoea 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Surgical and medical procedures
    Intramedullary rod insertion 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Vascular disorders
    Hypotension 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Other (Not Including Serious) Adverse Events
    40 mg TRC253/Daily 80 mg TRC253/Daily 160 mg TRC253/Daily 240 mg TRC253/Daily 280 mg TRC253/Daily 320 mg TRC253/Daily
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/1 (100%) 1/1 (100%) 2/2 (100%) 7/7 (100%) 48/51 (94.1%) 10/10 (100%)
    Blood and lymphatic system disorders
    Anaemia 0/1 (0%) 1/1 (100%) 1/2 (50%) 2/7 (28.6%) 8/51 (15.7%) 2/10 (20%)
    Thrombocytopenia 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/7 (14.3%) 2/51 (3.9%) 0/10 (0%)
    Splenic infarction 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Cardiac disorders
    Bradycardia 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Sinus tachycardia 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Tachycardia 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Coronary artery occlusion 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 0/51 (0%) 1/10 (10%)
    Ear and labyrinth disorders
    Vertigo 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/7 (14.3%) 0/51 (0%) 0/10 (0%)
    Tinnitus 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 0/51 (0%) 1/10 (10%)
    Endocrine disorders
    Hypothyroidism 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 0/51 (0%) 1/10 (10%)
    Eye disorders
    Diplopia 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/7 (14.3%) 0/51 (0%) 0/10 (0%)
    Eye discharge 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/7 (14.3%) 0/51 (0%) 0/10 (0%)
    Eyelid ptosis 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/7 (14.3%) 0/51 (0%) 0/10 (0%)
    Corneal neovascularisation 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Eye swelling 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Vitreous haemorrhage 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Gastrointestinal disorders
    Constipation 0/1 (0%) 1/1 (100%) 0/2 (0%) 1/7 (14.3%) 8/51 (15.7%) 4/10 (40%)
    Gingival bleeding 0/1 (0%) 1/1 (100%) 0/2 (0%) 0/7 (0%) 0/51 (0%) 0/10 (0%)
    Vomiting 0/1 (0%) 1/1 (100%) 1/2 (50%) 2/7 (28.6%) 6/51 (11.8%) 3/10 (30%)
    Abdominal pain 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/7 (0%) 6/51 (11.8%) 2/10 (20%)
    Nausea 0/1 (0%) 0/1 (0%) 1/2 (50%) 1/7 (14.3%) 9/51 (17.6%) 4/10 (40%)
    Ascites 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/7 (14.3%) 0/51 (0%) 0/10 (0%)
    Diarrhoea 0/1 (0%) 0/1 (0%) 0/2 (0%) 2/7 (28.6%) 10/51 (19.6%) 1/10 (10%)
    Eructation 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/7 (14.3%) 0/51 (0%) 0/10 (0%)
    Haematochezia 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/7 (14.3%) 0/51 (0%) 0/10 (0%)
    Abdominal discomfort 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Abdominal distension 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Dry mouth 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Flatulence 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Gastrooesophageal reflux disease 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    General disorders
    Fatigue 0/1 (0%) 1/1 (100%) 1/2 (50%) 1/7 (14.3%) 9/51 (17.6%) 6/10 (60%)
    Pyrexia 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/7 (0%) 3/51 (5.9%) 1/10 (10%)
    Temperature intolerance 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/7 (0%) 0/51 (0%) 0/10 (0%)
    Facial pain 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/7 (14.3%) 0/51 (0%) 0/10 (0%)
    Pain 0/1 (0%) 0/1 (0%) 0/2 (0%) 3/7 (42.9%) 0/51 (0%) 0/10 (0%)
    Asthenia 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 3/51 (5.9%) 2/10 (20%)
    Chills 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Gait disturbance 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Oedema peripheral 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 4/51 (7.8%) 2/10 (20%)
    Non-cardiac chest pain 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 1/10 (10%)
    Infections and infestations
    Lung infection 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/7 (0%) 0/51 (0%) 1/10 (10%)
    Acute sinusitis 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/7 (14.3%) 0/51 (0%) 0/10 (0%)
    Device related infection 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/7 (14.3%) 0/51 (0%) 0/10 (0%)
    Genital infection fungal 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/7 (14.3%) 0/51 (0%) 0/10 (0%)
    Oral herpes 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/7 (14.3%) 0/51 (0%) 0/10 (0%)
    Abscess 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Bronchitis 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Pyelonephritis acute 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Sinusitis 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 2/51 (3.9%) 0/10 (0%)
    Upper respiratory tract infection 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 6/51 (11.8%) 0/10 (0%)
    Urinary tract infection 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 5/51 (9.8%) 0/10 (0%)
    Staphylococcal infection 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 0/51 (0%) 1/10 (10%)
    Nasopharyngitis 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 0/51 (0%) 1/10 (10%)
    Injury, poisoning and procedural complications
    Fractured sacrum 0/1 (0%) 1/1 (100%) 0/2 (0%) 0/7 (0%) 0/51 (0%) 0/10 (0%)
    Clavicle fracture 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/7 (14.3%) 0/51 (0%) 0/10 (0%)
    Fall 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/7 (14.3%) 3/51 (5.9%) 1/10 (10%)
    Hip Fracture 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Rib fracture 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 2/51 (3.9%) 0/10 (0%)
    Investigations
    Blood alkaline phosphatase increased 0/1 (0%) 1/1 (100%) 1/2 (50%) 1/7 (14.3%) 3/51 (5.9%) 0/10 (0%)
    Electrocardiogram QT prolonged 0/1 (0%) 1/1 (100%) 1/2 (50%) 3/7 (42.9%) 14/51 (27.5%) 5/10 (50%)
    Platelet count decreased 0/1 (0%) 1/1 (100%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Weight decreased 0/1 (0%) 1/1 (100%) 1/2 (50%) 0/7 (0%) 5/51 (9.8%) 0/10 (0%)
    White blood cell count decreased 0/1 (0%) 1/1 (100%) 0/2 (0%) 0/7 (0%) 2/51 (3.9%) 0/10 (0%)
    White blood cell count increased 0/1 (0%) 1/1 (100%) 0/2 (0%) 0/7 (0%) 0/51 (0%) 0/10 (0%)
    Lipase increased 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/7 (14.3%) 0/51 (0%) 1/10 (10%)
    Lymphocyte count decreased 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/7 (14.3%) 0/51 (0%) 0/10 (0%)
    Alanine aminotransferase increased 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Aspartate aminotransferase increased 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 2/51 (3.9%) 2/10 (20%)
    Blood creatinine increased 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 5/51 (9.8%) 1/10 (10%)
    Blood thyroid stimulating hormone increased 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Blood amylase increased 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 0/51 (0%) 1/10 (10%)
    Lipase increased 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 0/51 (0%) 1/10 (10%)
    Metabolism and nutrition disorders
    Decreased appetite 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/7 (0%) 7/51 (13.7%) 2/10 (20%)
    Hypertriglyceridaemia 0/1 (0%) 0/1 (0%) 1/2 (50%) 1/7 (14.3%) 0/51 (0%) 0/10 (0%)
    Hypoalbuminaemia 0/1 (0%) 0/1 (0%) 1/2 (50%) 1/7 (14.3%) 0/51 (0%) 0/10 (0%)
    Hyponatraemia 0/1 (0%) 0/1 (0%) 1/2 (50%) 1/7 (14.3%) 2/51 (3.9%) 0/10 (0%)
    Acidosis 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/7 (14.3%) 0/51 (0%) 0/10 (0%)
    Hypophosphataemia 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/7 (14.3%) 3/51 (5.9%) 0/10 (0%)
    Dehydration 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 3/51 (5.9%) 0/10 (0%)
    Hyperkalaemia 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Hypocalcaemia 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 2/51 (3.9%) 0/10 (0%)
    Hyperglycaemia 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 0/51 (0%) 1/10 (10%)
    Hypermagnesaemia 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 0/51 (0%) 1/10 (10%)
    Hypokalaemia 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 0/51 (0%) 1/10 (10%)
    Hypomagnesaemia 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/7 (14.3%) 0/51 (0%) 1/10 (10%)
    Musculoskeletal and connective tissue disorders
    Musculoskeletal pain 1/1 (100%) 0/1 (0%) 1/2 (50%) 0/7 (0%) 3/51 (5.9%) 1/10 (10%)
    Pain in extremity 1/1 (100%) 1/1 (100%) 0/2 (0%) 0/7 (0%) 4/51 (7.8%) 4/10 (40%)
    Arthralgia 0/1 (0%) 1/1 (100%) 1/2 (50%) 2/7 (28.6%) 5/51 (9.8%) 1/10 (10%)
    Bone Pain 0/1 (0%) 1/1 (100%) 0/2 (0%) 2/7 (28.6%) 3/51 (5.9%) 1/10 (10%)
    Muscular weakness 0/1 (0%) 1/1 (100%) 0/2 (0%) 1/7 (14.3%) 4/51 (7.8%) 0/10 (0%)
    Pathological fracture 0/1 (0%) 1/1 (100%) 0/2 (0%) 0/7 (0%) 0/51 (0%) 0/10 (0%)
    Back pain 0/1 (0%) 0/1 (0%) 1/2 (50%) 3/7 (42.9%) 8/51 (15.7%) 5/10 (50%)
    Flank pain 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/7 (0%) 2/51 (3.9%) 0/10 (0%)
    Neck pain 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Muscle spasms 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/7 (14.3%) 1/51 (2%) 1/10 (10%)
    Pain in jaw 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/7 (14.3%) 0/51 (0%) 0/10 (0%)
    Joint stiffness 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Musculoskeletal chest pain 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 5/51 (9.8%) 0/10 (0%)
    Myalgia 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 3/51 (5.9%) 1/10 (10%)
    Pelvic Pain 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer pain 0/1 (0%) 1/1 (100%) 0/2 (0%) 0/7 (0%) 0/51 (0%) 0/10 (0%)
    Lipoma 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Squamous cell carcinoma of skin 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 0/51 (0%) 1/10 (10%)
    Nervous system disorders
    Neuropathy peripheral 0/1 (0%) 1/1 (100%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Spinal cord compression 0/1 (0%) 1/1 (100%) 0/2 (0%) 1/7 (14.3%) 1/51 (2%) 0/10 (0%)
    Dizziness 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/7 (0%) 6/51 (11.8%) 2/10 (20%)
    Extrapyramidal disorder 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/7 (0%) 0/51 (0%) 0/10 (0%)
    Headache 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/7 (0%) 2/51 (3.9%) 1/10 (10%)
    Burning sensation 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/7 (14.3%) 0/51 (0%) 0/10 (0%)
    Hypoaesthesia 0/1 (0%) 0/1 (0%) 0/2 (0%) 2/7 (28.6%) 0/51 (0%) 0/10 (0%)
    Cerebrovascular accident 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Dysgeusia 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 3/51 (5.9%) 0/10 (0%)
    Hypogeusia 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Paraesthesia 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 2/51 (3.9%) 0/10 (0%)
    Paraparesis 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Presyncope 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 2/51 (3.9%) 0/10 (0%)
    Sciatica 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Syncope 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    VIIth nerve paralysis 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Restless legs syndrome 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 0/51 (0%) 1/10 (10%)
    Psychiatric disorders
    Anxiety 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Insomnia 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 3/51 (5.9%) 0/10 (0%)
    Agitation 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 0/51 (0%) 1/10 (10%)
    Renal and urinary disorders
    Haematuria 1/1 (100%) 0/1 (0%) 1/2 (50%) 0/7 (0%) 3/51 (5.9%) 0/10 (0%)
    Urinary incontinence 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Nocturia 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/7 (14.3%) 0/51 (0%) 0/10 (0%)
    Proteinuria 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/7 (14.3%) 0/51 (0%) 0/10 (0%)
    Acute kidney injury 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Hydronephrosis 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Micturition urgency 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Neurogenic Bladder 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Pollakiuria 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 1/10 (10%)
    Urinary retention 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Vesicocutaneous fistula 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Dysuria 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 0/51 (0%) 1/10 (10%)
    Reproductive system and breast disorders
    Gynaecomastia 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Respiratory, thoracic and mediastinal disorders
    Epistaxis 0/1 (0%) 0/1 (0%) 1/2 (50%) 2/7 (28.6%) 0/51 (0%) 1/10 (10%)
    Oropharyngeal pain 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/7 (0%) 0/51 (0%) 1/10 (10%)
    Pneumonia 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/7 (0%) 1/51 (2%) 1/10 (10%)
    Dyspnoea 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/7 (14.3%) 2/51 (3.9%) 2/10 (20%)
    Productive cough 0/1 (0%) 0/1 (0%) 0/2 (0%) 2/7 (28.6%) 0/51 (0%) 1/10 (10%)
    Respiratory disorder 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/7 (14.3%) 1/51 (2%) 0/10 (0%)
    Cough 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 6/51 (11.8%) 2/10 (20%)
    Hiccups 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Hypoxia 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Pleural effusion 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 2/51 (3.9%) 1/10 (10%)
    Pneumonia aspiration 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Rhinorrhoea 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Sinus congestion 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Haemoptysis 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 0/51 (0%) 1/10 (10%)
    Skin and subcutaneous tissue disorders
    Dry skin 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/7 (0%) 3/51 (5.9%) 0/10 (0%)
    Pain of skin 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/7 (0%) 0/51 (0%) 0/10 (0%)
    Rash pruritic 0/1 (0%) 0/1 (0%) 1/2 (50%) 0/7 (0%) 0/51 (0%) 0/10 (0%)
    Alopecia 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Ecchymosis 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Night sweats 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Onychomadesis 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Petechiae 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Rash 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 2/51 (3.9%) 1/10 (10%)
    Dermatitis acneiform 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 0/51 (0%) 1/10 (10%)
    Dermatitis contact 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 0/51 (0%) 1/10 (10%)
    Dermatitis 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 0/51 (0%) 1/10 (10%)
    Hyperhidrosis 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 0/51 (0%) 1/10 (10%)
    Rash maculo-papular 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 0/51 (0%) 1/10 (10%)
    Urticaria 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 0/51 (0%) 1/10 (10%)
    Vascular disorders
    Hot flush 0/1 (0%) 0/1 (0%) 0/2 (0%) 1/7 (14.3%) 0/51 (0%) 0/10 (0%)
    Deep vein thrombosis 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Hypertension 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 3/51 (5.9%) 0/10 (0%)
    Hypotension 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 5/51 (9.8%) 1/10 (10%)
    Subclavian artery thrombosis 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 1/51 (2%) 0/10 (0%)
    Orthostatic hypotension 0/1 (0%) 0/1 (0%) 0/2 (0%) 0/7 (0%) 2/51 (3.9%) 1/10 (10%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Charles Theuer, MD PhD
    Organization Tracon Pharmaceuticals Inc.
    Phone 8585500780
    Email ctheuer@traconpharma.com
    Responsible Party:
    Tracon Pharmaceuticals Inc.
    ClinicalTrials.gov Identifier:
    NCT02987829
    Other Study ID Numbers:
    • 253PC101
    First Posted:
    Dec 9, 2016
    Last Update Posted:
    Apr 23, 2021
    Last Verified:
    Mar 1, 2021