Trial Outcomes & Findings for ENLIGHTEN: Establishing Novel Antiretroviral (ARV) Imaging for Hair to Elucidate Non-Adherence (NCT NCT03218592)

Last Updated: 2019-11-22

Results Overview

Signal Strength concentrations will be measured in hair for all study drugs, inclusive of FTC (emtricitabine), tenofovir (TFV), maraviroc (MRV), and dolutegravir (DTG) using Matrix-assisted Laser Desorption Electrospray Ionization (IR-MALDESI) to be reported by signal abundance (au). Signal abundance is the industry standard unit, and higher values represent greater signal with capability to relate to comparative concentrations.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

36 participants

Primary outcome timeframe

Up to 28 days post dose

Results posted on

2019-11-22

Participant Flow

Participant milestones

Participant milestones
Measure	Maraviroc 12 Healthy subjects will dose with Maraviroc Pill and we will collect blood and hair over all three phases Maraviroc Pill: Subjects will take a single dose in Phase 1, Daily Doses in Phase 2 for 28 days, and then be randomized in Phase 3 to zero doses, one dose a week or three doses weekly	Dolutegravir 12 Healthy volunteers will dose with Dolutegravir Pill and we will collect blood and hair over all three phases Dolutegravir Pill: Subjects will take a single dose in Phase 1, Daily Doses in Phase 2 for 28 days, and then be randomized in Phase 3 to zero doses, one dose a week or three doses weekly	Truvada 12 healthy volunteers will dose with Truvada Pill and we will collect blood and hair over all three phases Truvada Pill: Subjects will take a single dose in Phase 1, Daily Doses in Phase 2 for 28 days, and then be randomized in Phase 3 to zero doses, one dose a week or three doses weeklySubjects will take a single dose in Phase 1, Daily Doses in Phase 2 for 28 days, and then be randomized in Phase 3 to zero doses, one dose a week or three doses weekly
Phase 1: 1 Dose STARTED	12	12	12
Phase 1: 1 Dose COMPLETED	12	12	12
Phase 1: 1 Dose NOT COMPLETED	0	0	0
Phase 2: Daily Doses x 28 Days STARTED	12	12	12
Phase 2: Daily Doses x 28 Days COMPLETED	12	12	12
Phase 2: Daily Doses x 28 Days NOT COMPLETED	0	0	0
Phase 3: 0 Doses Per Week STARTED	4	4	4
Phase 3: 0 Doses Per Week 4 Patients Per Group	4	4	4
Phase 3: 0 Doses Per Week COMPLETED	4	4	4
Phase 3: 0 Doses Per Week NOT COMPLETED	0	0	0
Phase 3: 1 Dose Per Period STARTED	4	4	4
Phase 3: 1 Dose Per Period 4 Patients Per Group	4	4	4
Phase 3: 1 Dose Per Period COMPLETED	4	4	4
Phase 3: 1 Dose Per Period NOT COMPLETED	0	0	0
Phase 3: 3 Doses Per Week STARTED	4	4	4
Phase 3: 3 Doses Per Week 4 Patients Per Group	4	4	4
Phase 3: 3 Doses Per Week COMPLETED	4	4	4
Phase 3: 3 Doses Per Week NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

ENLIGHTEN: Establishing Novel Antiretroviral (ARV) Imaging for Hair to Elucidate Non-Adherence

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: Up to 28 days post dose

Population: In Phase 3, the 12 participants were divided into 3 dosing categories: either zero further doses,1 dose per week, or 3 doses per week. For the single dose Phase 1, signal abundance was not able to be observed consistently for all drug arms

Outcome measures

Outcome measures
Measure	Maraviroc n=12 Participants 12 Healthy subjects will dose with Maraviroc Pill and we will collect blood and hair over all three phases Maraviroc Pill: Subjects will take a single dose in Phase 1, Daily Doses in Phase 2 for 28 days, and then be randomized in Phase 3 to zero doses, one dose a week or three doses weekly	Dolutegravir n=12 Participants 12 Healthy volunteers will dose with Dolutegravir Pill and we will collect blood and hair over all three phases Dolutegravir Pill: Subjects will take a single dose in Phase 1, Daily Doses in Phase 2 for 28 days, and then be randomized in Phase 3 to zero doses, one dose a week or three doses weekly	Truvada n=12 Participants 12 healthy volunteers will dose with Truvada Pill and we will collect blood and hair over all three phases Truvada Pill: Subjects will take a single dose in Phase 1, Daily Doses in Phase 2 for 28 days, and then be randomized in Phase 3 to zero doses, one dose a week or three doses weekly. Subjects will take a single dose in Phase 1, Daily Doses in Phase 2 for 28 days, and then be randomized in Phase 3 to zero doses, one dose a week or three doses weekly.	Emtricitabine (Truvada) 2nd Component in the combo pill Truvada
Hair Antiretroviral Imaging Phase 3: Zero Doses Per Week	156.4826656 Signal Abundance (au) Interval 112.6510968 to 180.8064285	1092.130868 Signal Abundance (au) Interval 688.7225983 to 1325.75008	0.501209 Signal Abundance (au) Interval 0.2506045 to 11.540693	—
Hair Antiretroviral Imaging Phase 3: 1 Dose Per week	3942.692396 Signal Abundance (au) Interval 1054.128706 to 7097.7465	2377.868226 Signal Abundance (au) Interval 1241.605663 to 3519.225695	156.1127125 Signal Abundance (au) Interval 123.2479595 to 177.8878063	—
Hair Antiretroviral Imaging Phase 3: 3 Doses Per Week	27814.98823 Signal Abundance (au) Interval 7059.467332 to 47573.27029	5504.883169 Signal Abundance (au) Interval 3993.758552 to 6547.002816	466.7986895 Signal Abundance (au) Interval 416.4048878 to 517.1924913	—
Hair Antiretroviral Imaging Phase 2: Daily Dosing	46013.29104 Signal Abundance (au) Interval 14567.14721 to 62292.81721	14251.46653 Signal Abundance (au) Interval 7003.462543 to 18357.12725	824.721385 Signal Abundance (au) Interval 593.842582 to 1378.448229	—
Hair Antiretroviral Imaging Phase 1: Single Dose	NA Signal Abundance (au) Interval 0.0 to 0.0 For the single dose Phase 1, signal abundance was not able to be observed consistently for all drug arms	NA Signal Abundance (au) Interval 0.0 to 0.0 For the single dose Phase 1, signal abundance was not able to be observed consistently for all drug arms	NA Signal Abundance (au) Interval 0.0 to 0.0 For the single dose Phase 1, signal abundance was not able to be observed consistently for all drug arms	—

SECONDARY outcome

Timeframe: Up to 28 days post-dose

Population: PBMC Concentrations were analyzed in the Truvada arm only. Results are for emtricitabine-triphosphate.

Concentrations of emtricitabine-triphosphate, tenofovir-diphosphate will be measured in peripheral blood mononuclear cells in the Truvada arm only. Truvada is a combination pill, so results for both FTC and TFV are reported in separate columns.

Outcome measures

Outcome measures
Measure	Maraviroc 12 Healthy subjects will dose with Maraviroc Pill and we will collect blood and hair over all three phases Maraviroc Pill: Subjects will take a single dose in Phase 1, Daily Doses in Phase 2 for 28 days, and then be randomized in Phase 3 to zero doses, one dose a week or three doses weekly	Dolutegravir 12 Healthy volunteers will dose with Dolutegravir Pill and we will collect blood and hair over all three phases Dolutegravir Pill: Subjects will take a single dose in Phase 1, Daily Doses in Phase 2 for 28 days, and then be randomized in Phase 3 to zero doses, one dose a week or three doses weekly	Truvada n=12 Participants 12 healthy volunteers will dose with Truvada Pill and we will collect blood and hair over all three phases Truvada Pill: Subjects will take a single dose in Phase 1, Daily Doses in Phase 2 for 28 days, and then be randomized in Phase 3 to zero doses, one dose a week or three doses weekly. Subjects will take a single dose in Phase 1, Daily Doses in Phase 2 for 28 days, and then be randomized in Phase 3 to zero doses, one dose a week or three doses weekly.	Emtricitabine (Truvada) n=12 Participants 2nd Component in the combo pill Truvada
Peripheral Blood Mononuclear Cells (PBMC) Antiretroviral Concentrations Phase 1 Single Dose	—	—	2.1 fmol/10^6 cells Interval 1.2 to 18.5	27.09 fmol/10^6 cells Interval 1.74 to 465.7
Peripheral Blood Mononuclear Cells (PBMC) Antiretroviral Concentrations Phase 2: 7 Doses per Week	—	—	127.1 fmol/10^6 cells Interval 101.0 to 185.0	4460 fmol/10^6 cells Interval 3620.0 to 5930.0
Peripheral Blood Mononuclear Cells (PBMC) Antiretroviral Concentrations Phase 3: 3 Doses Per Week	—	—	60 fmol/10^6 cells Interval 54.6 to 71.8	2388.69 fmol/10^6 cells Interval 1341.4 to 3071.35
Peripheral Blood Mononuclear Cells (PBMC) Antiretroviral Concentrations Phase 3: 1 Dose Per Week	—	—	15.7 fmol/10^6 cells Interval 12.2 to 24.2	267.82 fmol/10^6 cells Interval 194.49 to 453.27
Peripheral Blood Mononuclear Cells (PBMC) Antiretroviral Concentrations Phase 3: Zero Doses per week	—	—	10.4 fmol/10^6 cells Interval 3.5 to 18.5	27.48 fmol/10^6 cells Interval 1.11 to 135.28

SECONDARY outcome

Timeframe: Up to 28 days post-dose

Population: 3 drug arms, but Truvada is inclusive of both TFV-dp and FTC-tp

Concentrations will be measured in hair of all study drugs, inclusive of FTC (emtricitabine), TFV (tenofovir), MRV (Maraviroc), and DTG (dolutegravir)

Outcome measures

Outcome measures
Measure	Maraviroc n=12 Participants 12 Healthy subjects will dose with Maraviroc Pill and we will collect blood and hair over all three phases Maraviroc Pill: Subjects will take a single dose in Phase 1, Daily Doses in Phase 2 for 28 days, and then be randomized in Phase 3 to zero doses, one dose a week or three doses weekly	Dolutegravir n=12 Participants 12 Healthy volunteers will dose with Dolutegravir Pill and we will collect blood and hair over all three phases Dolutegravir Pill: Subjects will take a single dose in Phase 1, Daily Doses in Phase 2 for 28 days, and then be randomized in Phase 3 to zero doses, one dose a week or three doses weekly	Truvada n=12 Participants 12 healthy volunteers will dose with Truvada Pill and we will collect blood and hair over all three phases Truvada Pill: Subjects will take a single dose in Phase 1, Daily Doses in Phase 2 for 28 days, and then be randomized in Phase 3 to zero doses, one dose a week or three doses weekly. Subjects will take a single dose in Phase 1, Daily Doses in Phase 2 for 28 days, and then be randomized in Phase 3 to zero doses, one dose a week or three doses weekly.	Emtricitabine (Truvada) n=12 Participants 2nd Component in the combo pill Truvada
Plasma Antiretroviral Concentrations Phase 1: Single dose	1 ng/mL Interval 1.0 to 1.0	1 ng/mL Interval 1.0 to 3.455	0.5 ng/mL Interval 0.5 to 0.5	0.5 ng/mL Interval 0.5 to 1.2
Plasma Antiretroviral Concentrations Phase2: 7 Doses per Week	9.715 ng/mL Interval 7.765 to 12.575	1240 ng/mL Interval 797.0 to 1555.0	61.9 ng/mL Interval 51.1 to 72.9	72.3 ng/mL Interval 60.3 to 91.4
Plasma Antiretroviral Concentrations Phase 3: 3 Doses Per Week	1.71 ng/mL Interval 1.18775 to 3.955	69.3 ng/mL Interval 31.4 to 155.0	9.4 ng/mL Interval 6.6 to 45.3	17.2 ng/mL Interval 8.8 to 57.8
Plasma Antiretroviral Concentrations Phase 3: 1 Dose Per Week	1 ng/mL Interval 1.0 to 1.0	3.095 ng/mL Interval 1.4175 to 5.875	0.5 ng/mL Interval 0.5 to 0.7	1.2 ng/mL Interval 0.9 to 1.9
Plasma Antiretroviral Concentrations Phase 3: 0 Doses per week	1 ng/mL Interval 1.0 to 1.0	1 ng/mL Interval 1.0 to 1.2725	0.5 ng/mL Interval 0.5 to 0.5	0.5 ng/mL Interval 0.5 to 0.8

SECONDARY outcome

Timeframe: Up to 28 days post-dose

Population: 3 drug arms, but Truvada is inclusive of both TFV/FTC so reported here separately

Concentrations will be measured in dried blood spots of all study drugs, inclusive of FTC (emtricitabine), TFV (tenofovir), MRV (Maraviroc), and DTG (dolutegravir). Truvada is a combination pill, so results for both FTC and TFV are reported in separate columns.

Outcome measures

Outcome measures
Measure	Maraviroc n=12 Participants 12 Healthy subjects will dose with Maraviroc Pill and we will collect blood and hair over all three phases Maraviroc Pill: Subjects will take a single dose in Phase 1, Daily Doses in Phase 2 for 28 days, and then be randomized in Phase 3 to zero doses, one dose a week or three doses weekly	Dolutegravir n=12 Participants 12 Healthy volunteers will dose with Dolutegravir Pill and we will collect blood and hair over all three phases Dolutegravir Pill: Subjects will take a single dose in Phase 1, Daily Doses in Phase 2 for 28 days, and then be randomized in Phase 3 to zero doses, one dose a week or three doses weekly	Truvada n=12 Participants 12 healthy volunteers will dose with Truvada Pill and we will collect blood and hair over all three phases Truvada Pill: Subjects will take a single dose in Phase 1, Daily Doses in Phase 2 for 28 days, and then be randomized in Phase 3 to zero doses, one dose a week or three doses weekly. Subjects will take a single dose in Phase 1, Daily Doses in Phase 2 for 28 days, and then be randomized in Phase 3 to zero doses, one dose a week or three doses weekly.	Emtricitabine (Truvada) n=12 Participants 2nd Component in the combo pill Truvada
Whole Blood Antiretroviral Concentrations Phase 3: 0 Doses per week	3 fmol / 3mm punch Interval 3.0 to 3.0	10 fmol / 3mm punch Interval 10.0 to 12.5	621 fmol / 3mm punch Interval 433.5 to 906.0	50 fmol / 3mm punch Interval 50.0 to 50.0
Whole Blood Antiretroviral Concentrations Phase 1: Single Dose	3 fmol / 3mm punch Interval 3.0 to 3.0	10 fmol / 3mm punch Interval 10.0 to 20.0	50 fmol / 3mm punch Interval 50.0 to 50.0	50 fmol / 3mm punch Interval 50.0 to 50.0
Whole Blood Antiretroviral Concentrations Phase 2: 7 Doses per Week	9.185 fmol / 3mm punch Interval 7.76 to 11.625	718.5 fmol / 3mm punch Interval 482.5 to 937.75	809.5 fmol / 3mm punch Interval 504.8 to 1107.5	280 fmol / 3mm punch Interval 214.2 to 345.7
Whole Blood Antiretroviral Concentrations Phase 3: 3 Doses Per Week	3 fmol / 3mm punch Interval 3.0 to 4.2025	60.95 fmol / 3mm punch Interval 39.0 to 166.75	811 fmol / 3mm punch Interval 698.0 to 1027.5	150.5 fmol / 3mm punch Interval 50.0 to 221.3
Whole Blood Antiretroviral Concentrations Phase 3: 1 Dose Per Week	3 fmol / 3mm punch Interval 3.0 to 3.0	10 fmol / 3mm punch Interval 10.0 to 20.0	644.5 fmol / 3mm punch Interval 598.2 to 1007.5	50 fmol / 3mm punch Interval 50.0 to 50.0

Adverse Events

Maraviroc

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Dolutegravir

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Truvada

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Angela Kashuba

University of North Carolina at Chapel Hill

Phone: 9199969998

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Maraviroc n=12 Participants 12 Healthy subjects will dose with Maraviroc Pill and we will collect blood and hair over all three phases Maraviroc Pill: Subjects will take a single dose in Phase 1, Daily Doses in Phase 2 for 28 days, and then be randomized in Phase 3 to zero doses, one dose a week or three doses weekly	Dolutegravir n=12 Participants 12 Healthy volunteers will dose with Dolutegravir Pill and we will collect blood and hair over all three phases Dolutegravir Pill: Subjects will take a single dose in Phase 1, Daily Doses in Phase 2 for 28 days, and then be randomized in Phase 3 to zero doses, one dose a week or three doses weekly	Truvada n=12 Participants 12 healthy volunteers will dose with Truvada (TFV/FTC) Pill and we will collect blood and hair over all three phases Truvada Pill: Subjects will take a single dose in Phase 1, Daily Doses in Phase 2 for 28 days, and then be randomized in Phase 3 to zero doses, one dose a week or three doses weekly. Subjects will take a single dose in Phase 1, Daily Doses in Phase 2 for 28 days, and then be randomized in Phase 3 to zero doses, one dose a week or three doses weekly	Total n=36 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	12 Participants n=5 Participants	12 Participants n=7 Participants	12 Participants n=5 Participants	36 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Continuous	31 years n=5 Participants	42 years n=7 Participants	26.5 years n=5 Participants	32 years n=4 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	9 Participants n=7 Participants	10 Participants n=5 Participants	29 Participants n=4 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	7 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=5 Participants	12 Participants n=7 Participants	11 Participants n=5 Participants	32 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	4 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) White	10 Participants n=5 Participants	11 Participants n=7 Participants	8 Participants n=5 Participants	29 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment United States	12 Participants n=5 Participants	12 Participants n=7 Participants	12 Participants n=5 Participants	36 Participants n=4 Participants
Healthy Volunteer Status	12 Participants n=5 Participants	12 Participants n=7 Participants	12 Participants n=5 Participants	36 Participants n=4 Participants