Pharmacokinetics and Safety Study of Siremadlin (HDM201) in Participants With Mild, Moderate and Severe Hepatic Impairment
Condition: Hepatic Impairment
MeSH terms: Liver Diseases
Study type: Interventional
Phase: Phase 1

Summary: 
      The main purpose of this study is to evaluate the effect of varying degrees of impaired
      hepatic function (by Child Pugh classification) on the plasma PK of siremadlin after a single
      oral dose. In addition, safety and tolerability of siremadlin after a single oral dose will
      be evaluated. The results of this study will inform the decision whether a dose adjustment
      may be recommended when treating patients with various degrees of impaired hepatic function.
    

Detailed description: 
      Participants will be recruited into one of 4 groups according to the Child-Pugh
      classification score. Participants with HI will be enrolled into either mild (Child-Pugh A;
      Group 2), moderate (Child Pugh B; Group 3) or severe (Child-Pugh C; Group 4) HI groups.
      Healthy control participants (Group 1) will be matched to 1 or more participants with HI with
      respect to age (± 10 years), body weight (± 20%) and sex. Each participant in the matched
      healthy control group (Group 1) can be matched to participant(s) in any HI group (Groups 2,
      3, and 4).

      The study will enroll the four groups in parallel. Therefore, enrollment in Group 1 will
      remain open until enrollment in the mild, moderate and severe HI groups is complete and each
      HI participant has a matched healthy control (Group 1) participant. Participants from Group 1
      will be enrolled after at least 3 participants from each of Groups 2 and 3 have completed all
      scheduled assessments.

      The study consists of a screening period of up to 28 days (Days -29 to -2), a baseline
      evaluation on Day -1, a single dose administration of siremadlin on Day 1 followed by PK
      sampling up to 144 hours post-dose (Day 7). All baseline safety evaluation results must be
      available and reviewed prior to the dosing. All eligible participants will be domiciled from
      Day -1 until Day 7.

      Safety assessments will include physical examinations, ECGs, vital signs, standard clinical
      laboratory evaluations (hematology, blood chemistry, urinalysis, coagulation), AE and serious
      adverse event (SAE) monitoring.

      All participants will have a post-study safety follow-up contact conducted approximately 30
      days after administration of study treatment. The study will be considered complete once all
      the participants have finished the required assessments, dropped out, or been lost to
      follow-up before completing the required assessments.

      The total study duration for each participant is expected to be up to maximum of 59 days,
      including the Screening period and the 30-day post-study safety contact follow up period.
    

Intervention name(s): Siremadlin
Intervention type(s): Drug
Intervention description(s): HDM201 capsule
Other intervention name(s): HDM201
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Hepatic Impairment; Solids tumors; Hematological malignancies; Child-Pugh classification; HDM201; Siremadlin