Apretude Adverse Reactions

Clinical trial data: Adverse drug reactions (ADRs) for cabotegravir were identified from the Phase III clinical studies, HPTN 083 and HPTN 084. In HPTN 083, the median time on blinded study product was 65 weeks and 2 days (1 day to 156 weeks and 1 day), with a total exposure on cabotegravir of 3270 person years. In HPTN 084, the median time on blinded study product was 64 weeks and 1 day (1 day to 153 weeks and 1 day), with a total exposure on cabotegravir of 1920 person years.
ADRs listed include those attributable to the oral or injectable formulations of cabotegravir. When frequencies differed between HPTN 083 and 084, the highest frequency category is quoted.
The most frequently reported ADRs in HPTN 083 were: Injection site reactions (82%), headache (17%), and diarrhoea (14%).
The most frequently reported ADRs in HPTN 084 were: Injection site reactions (38%), headache (23%), and transaminase increased (19%).
The ADRs identified in these studies are listed as follows by MedDRA system organ class and by frequency. Frequencies are defined as: very common (≥1/10), common (≥1/100 and <1/10), uncommon (≥1/1,000 and <1/100), rare (≥1/10,000 and <1/1,000) and very rare (<1/10,000), including isolated reports. (See Table 10.)

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Local Injection Site Reactions: In HPTN 083, 2% of participants discontinued cabotegravir because of ISRs.
Out of 20286 injections, 8900 ISRs were reported.
A total of 2117 participants received at least one injection. Of the 1740 (82%) participants who experienced at least one ISR, the maximum severity of ISRs reported was mild (Grade 1, 34% of participants), moderate (Grade 2, 46% of participants), or severe (Grade 3, 3% of participants). No participants experienced Grade 4 ISRs. The median duration of overall ISR events was 4 days. The proportion of participants reporting ISRs at each visit and the severity of the ISRs decreased over time.
In HPTN 084, no participants discontinued cabotegravir because of ISRs.
Out of 13068 injections, 1171 ISRs were reported.
A total of 1519 participants received at least one injection. Of the 578 (38%) participants who experienced at last one ISR, the maximum severity of ISRs reported was mild (Grade 1, 25% of participants), moderate (Grade 2, 13% of participants), or severe (Grade 3, <1% of participants). No participants experienced Grade 4 ISRs. The median duration of overall ISR events was 8 days. The proportion of participants reporting ISRs at each visit and the severity of the ISRs generally decreased over time.
Weight increased: At the Week 41 and 97 timepoints in HPTN 083, participants who received cabotegravir gained a median of 1.2 kg (IQR -1.0, 3.5; n=1623) and 2.1 kg (IQR; -0.9, 5.9 n=601) in weight from baseline, respectively; those in the tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) group gained a median of 0.0 kg (IQR -2.1, 2.4, n=1611) and 1.0 kg (IQR; -1.9, 4.0 n=598) in weight from baseline, respectively.
At the Week 41 and 97 timepoints in HPTN 084, participants who received cabotegravir gained a median of 2.0 kg (IQR 0.0, 5.0; n=1151) and 4.0 kg (IQR; 0.0, 8.0, n=216) in weight from baseline, respectively; those in the tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) group gained a median of 1.0 kg (IQR -1.0, 4.0, n=1131) and 3.0 kg (IQR; -1.0, 6.0 n=218) in weight from baseline, respectively.
Changes in laboratory chemistries: In both HPTN 083 and HPTN 084, a similar proportion of participants in the cabotegravir and TDF/FTC groups were observed to have elevated hepatic transaminases (ALT/AST) levels and maximum post baseline increases were mostly Grades 1 and 2. In HPTN 083, the number of participants in the cabotegravir vs TDF/FTC groups who experienced maximum post baseline Grade 3 or 4 ALT levels were 40 (2%) vs 44 (2%) and Grade 3 or 4 AST levels were; 68 (3%) vs 79 (3%), respectively. In HPTN 084, the number of participants in the cabotegravir vs TDF/FTC groups who experienced maximum post baseline Grade 3 or 4 ALT levels were 12 (<1%) vs 18 (1%) and Grade 3 and 4 AST levels were 15 (<1%) vs 14 (<1%), respectively.
A few participants in both the cabotegravir and TDF/FTC groups had adverse events of AST or ALT increased which resulted in discontinuation of study product. In HPTN 083, the number of participants in the cabotegravir vs TDF/FTC groups who discontinued due to ALT increased were 29 (1%) vs 31 (1%) and due to AST increased were 7 (<1%) vs 8 (<1%), respectively. In HPTN 084, the number of participants in the cabotegravir vs TDF/FTC groups who discontinued due to ALT increased were 12 (<1%) vs 15 (<1%) and there were no discontinuations due to AST increased.
Paediatric population: Based on data from two open-label multicentre clinical trials (HPTN 083-01 and HPTN 084-01) in 64 HIV-uninfected, at-risk adolescents (weighing 35 kg or more) receiving cabotegravir, no new safety concerns were identified in adolescents compared with the safety profile established in adults receiving cabotegravir for HIV-1 PrEP.
Based on data from the Week 16 analysis of the MOCHA study in HIV-infected adolescents (aged at least 12 years and weighing 35 kg or more) receiving background cART, no new safety concerns were identified in adolescents with the addition of oral cabotegravir followed by injectable cabotegravir (n=29) when compared with the safety profile established with cabotegravir in adults (see Pharmacology: Pharmacodynamics: Clinical Studies under Actions).
Post-marketing data: (See Table 11.)

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